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Pereira JG, Pontes TMB, Carvalho FMM, Gomes ABF, Erbisti RS, de Sousa Junior IP, Colares JKB, Lima DM, de Paula VS. Detection of Herpesviruses (Predominantly HHV-6) in Patients with Guillain-Barré Syndrome. Biomedicines 2025; 13:845. [PMID: 40299442 PMCID: PMC12025303 DOI: 10.3390/biomedicines13040845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/20/2025] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Guillain-Barré syndrome (GBS) is a neurological disease that affects the peripheral nerves. The exact cause of this condition is still uncertain, but cross-reactivity between pathogen antigens and nervous tissue may play a crucial role in disease pathogenesis. Roseolovirus humanbeta6 (HHV-6), a neurotropic virus with latency capacity, may be considered a significant candidate for triggering or worsening neurological conditions. In this study, we aimed to investigate the detection of HHV-6 in the CNS from GBS patients. Of the 23 individuals suspected of having GBS, 13 were confirmed as having the disease. We then analyzed the frequency of herpesviruses in the cerebrospinal fluid (CSF) samples from these 13 individuals with GBS who were also tested for enteroviruses and arboviruses and had negative results. Results: After extraction of viral DNA from CSF samples, real-time PCR (qPCR) methodology was used to analyze the frequency and viral load of herpesviruses. Sociodemographic and clinical data were collected for analysis and verification through statistical tests such as Fisher's exact test and the Mann-Whitney test. Thirteen individuals diagnosed with GBS were tested. Among the 13 patients analyzed, 61.5% were men, 38.4% (5/13) tested positive for HHV-6, 61.5% of the patients tested positive for a herpesvirus, 30.8% had two viral DNAs identified, and one patient presented three different strains. Patients who tested positive for HHV-6 had a significantly longer average length of stay (25.6 days versus 11 days for negative patients). HHV-6 was the most frequent subtype detected in patients positive for herpesviruses (62.5%, 5/8). Discussion/Conclusions: Our results show a possible relationship between HHV-6 and GBS cases despite the small number of patients, raising the question of whether the presence of HHV-6 influences GBS, since its investigation using qPCR is not routinely used. This may have some impact on prognosis, since antiviral therapy is not included in the standard treatment of GBS patients, and viral DNA load may interfere with the inflammatory process of GBS.
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Affiliation(s)
- Jéssica Gonçalves Pereira
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil; (J.G.P.); (I.P.d.S.J.)
| | - Tainá Madeira Barros Pontes
- Graduate Program in Medical Sciences, University of Fortaleza, Fortaleza 60811-905, Brazil; (T.M.B.P.); (F.M.M.C.); (A.B.F.G.); (J.K.B.C.)
| | - Fernanda Martins Maia Carvalho
- Graduate Program in Medical Sciences, University of Fortaleza, Fortaleza 60811-905, Brazil; (T.M.B.P.); (F.M.M.C.); (A.B.F.G.); (J.K.B.C.)
- Neurology Department, Fortaleza General Hospital, Fortaleza 60150-160, Brazil
| | - André Borges Ferreira Gomes
- Graduate Program in Medical Sciences, University of Fortaleza, Fortaleza 60811-905, Brazil; (T.M.B.P.); (F.M.M.C.); (A.B.F.G.); (J.K.B.C.)
- Neurology Department, Fortaleza General Hospital, Fortaleza 60150-160, Brazil
| | - Rafael Santos Erbisti
- Department of Statistics, Institute of Mathematics and Statistics, Fluminense Federal University, Niterói 24210-240, Brazil;
| | - Ivanildo Pedro de Sousa Junior
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil; (J.G.P.); (I.P.d.S.J.)
| | - Jeová Keny Baima Colares
- Graduate Program in Medical Sciences, University of Fortaleza, Fortaleza 60811-905, Brazil; (T.M.B.P.); (F.M.M.C.); (A.B.F.G.); (J.K.B.C.)
| | - Danielle Malta Lima
- Graduate Program in Medical Sciences, University of Fortaleza, Fortaleza 60811-905, Brazil; (T.M.B.P.); (F.M.M.C.); (A.B.F.G.); (J.K.B.C.)
| | - Vanessa Salete de Paula
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil; (J.G.P.); (I.P.d.S.J.)
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Talwar S, Harker JA, Openshaw PJM, Thwaites RS. Autoimmunity in long COVID. J Allergy Clin Immunol 2025; 155:1082-1094. [PMID: 39956285 DOI: 10.1016/j.jaci.2025.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/24/2025] [Accepted: 02/07/2025] [Indexed: 02/18/2025]
Abstract
Long COVID (also termed postacute sequelae of SARS-CoV-2, or PASC) affects up to 10% of people recovering from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, incomplete understanding of pathogenesis, and lack of validated treatments. In terms of pathogenesis, hypothesized causes include virus persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show preexisting and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long COVID.
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Affiliation(s)
- Shubha Talwar
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - James A Harker
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Peter J M Openshaw
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Ryan S Thwaites
- National Heart and Lung Institute, Imperial College London, London, United Kingdom.
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Nihei Y, Kitamura D. Pathogenesis of IgA nephropathy as a tissue-specific autoimmune disease. Int Immunol 2024; 37:75-81. [PMID: 39066568 DOI: 10.1093/intimm/dxae047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 07/26/2024] [Indexed: 07/28/2024] Open
Abstract
Glomerulonephritis (GN) is a group of heterogeneous immune-mediated kidney diseases that causes inflammation within the glomerulus. Autoantibodies (auto-Abs) are considered to be central effectors in the pathogenesis of several types of GN. Immunoglobulin A nephropathy (IgAN) is the most common GN worldwide and is characterized by the deposition of IgA in the glomerular mesangium of the kidneys, which is thought to be mediated by immune complexes containing non-specific IgA. However, we recently reported that IgA auto-Abs specific to mesangial cells (anti-mesangium IgA) were found in the sera of gddY mice, a spontaneous IgAN model, and patients with IgAN. We identified two autoantigens (β2-spectrin and CBX3) that are selectively expressed on the mesangial cell surface and targeted by anti-mesangial IgA. Our findings redefined IgAN as a tissue-specific autoimmune disease. Regarding the mechanisms of production of anti-mesangium IgA, studies using gddY mice have revealed that the production of anti-CBX3 IgA is induced by particular strains of commensal bacteria in the oral cavity, possibly through their molecular mimicry to CBX3. Here, we discuss a new concept of IgAN pathogenesis from the perspective of this disease as autoimmune GN caused by tissue-specific auto-Abs.
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Affiliation(s)
- Yoshihito Nihei
- Department of Nephrology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
- Division of Cancer Cell Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan
| | - Daisuke Kitamura
- Division of Cancer Cell Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan
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Tajik S, Farahani AV, Ardekani OS, Seyedi S, Tayebi Z, Kami M, Aghaei F, Hosseini TM, Nia MMK, Soheili R, Letafati A. Zika virus tropism and pathogenesis: understanding clinical impacts and transmission dynamics. Virol J 2024; 21:271. [PMID: 39472938 PMCID: PMC11523830 DOI: 10.1186/s12985-024-02547-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 10/17/2024] [Indexed: 11/02/2024] Open
Abstract
The Zika virus (ZIKV) is classified within the Flavivirus genus of the Flaviviridae family and is categorized as an arbovirus. The virus was initially identified in a rhesus monkey in Uganda in 1947 and later in a human in Nigeria in 1952. Since 2007, the prevalence of the virus has been on the rise, culminating in a major outbreak in the United States (US) in 2015. During this outbreak, the adult population was severely impacted, experiencing a range of symptoms, including organ failure, microcephaly, fetal death, and Guillain-Barré syndrome (GBS). Additionally, skin rash, limb swelling, fever, headache, and heightened sensitivity are found in most adults with Zika syndrome. Although the virus can be transmitted through blood, vertical transmission from mother to child, and sexual contact, the primary way of transmission of the virus is through the Aedes mosquito. Cells such as neurons, macrophages, peripheral dendritic cells, and placental cells are among the target cells that the virus can infect. The TAM AXL receptor plays a crucial role in infection. After the virus enters the body through the bloodstream, it spreads in the body with a latent period of 3 to 12 days. Currently, there is no specific treatment or publicly available vaccine for the ZIKV. Limited laboratory testing has been conducted, and existing drugs originally designed for other pathogens have been repurposed for treatment. Given the Aedes mosquito's role as a vector and the wide geographical impact of the virus, this study aims to comprehensively investigate Zika's pathogenesis and clinical symptoms based on existing knowledge and research. By doing so, we seek to enhance our understanding of the virus and inform future prevention and treatment strategies.
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Affiliation(s)
- Saeed Tajik
- Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Vasheghani Farahani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Zahra Tayebi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Microbiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mostafa Kami
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pathology, Faculty of Veterinary Medicine, Babol Branch, Islamic Azad University, Babol, Iran
| | - Faezeh Aghaei
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Mohammad Mahdi Khosravi Nia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Student Research Committee, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Roben Soheili
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arash Letafati
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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V S, Pattanaik A, Marate S, Mani RS, Pai AR, Mukhopadhyay C. Guillain-barré syndrome (GBS) with antecedent chikungunya infection: a case report and literature review. Neurol Res Pract 2024; 6:21. [PMID: 38600592 PMCID: PMC11008014 DOI: 10.1186/s42466-024-00315-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 03/04/2024] [Indexed: 04/12/2024] Open
Abstract
Guillain-Barré Syndrome (GBS) is an autoimmune neuropathy. Antecedent infections have been seen to be significant triggering factors for developing GBS. Among them, arboviral infections are rapidly gaining importance as significant triggers, especially in the areas where they are endemic. Chikungunya, an arboviral infection that usually causes a self-limiting acute febrile illness can lead to GBS as one its severe complications. Herein, we describe a case of a 21-year-old female who presented with weakness in all four limbs and paresthesia. Nerve conduction study and cerebrospinal fluid (CSF) analysis showed axonal, demyelinating motor and sensory neuropathy with albuminocytological dissociation indicating Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. Serum IgM antibodies against ganglioside GM1 were detected. Anti-Chikungunya IgM antibodies were found in both serum and CSF samples. The patient was initiated with Intravenous Immunoglobulin (IVIG) therapy. In view of hypoxia, she was intubated and was on mechanical ventilation. After 2 weeks of being comatose, the patient gradually improved and was discharged with no sequelae.A literature review on antecedent infections in GBS is presented alongside the case report to better understand the association of GBS with antecedent infections, especially the endemic arboviral infections like Chikungunya, Dengue and Zika. This will help in reinforcing the significance of having robust surveillance and public health control measures for infectious diseases.
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Affiliation(s)
- Sreelakshmi V
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Amrita Pattanaik
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
| | - Srilatha Marate
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Reeta S Mani
- Department of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Karnataka, Bengaluru, India
| | - Aparna R Pai
- Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
| | - Chiranjay Mukhopadhyay
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
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Martinelli S, Nannini G, Cianchi F, Coratti F, Amedei A. The Impact of Microbiota-Immunity-Hormone Interactions on Autoimmune Diseases and Infection. Biomedicines 2024; 12:616. [PMID: 38540229 PMCID: PMC10967803 DOI: 10.3390/biomedicines12030616] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 02/07/2025] Open
Abstract
Autoimmune diseases are complex multifactorial disorders, and a mixture of genetic and environmental factors play a role in their onset. In recent years, the microbiota has gained attention as it helps to maintain host health and immune homeostasis and is a relevant player in the interaction between our body and the outside world. Alterations (dysbiosis) in its composition or function have been linked to different pathologies, including autoimmune diseases. Among the different microbiota functions, there is the activation/modulation of immune cells that can protect against infections. However, if dysbiosis occurs, it can compromise the host's ability to protect against pathogens, contributing to the development and progression of autoimmune diseases. In some cases, infections can trigger autoimmune diseases by several mechanisms, including the alteration of gut permeability and the activation of innate immune cells to produce pro-inflammatory cytokines that recruit autoreactive T and B cells. In this complex scenario, we cannot neglect critical hormones' roles in regulating immune responses. Different hormones, especially estrogens, have been shown to influence the development and progression of autoimmune diseases by modulating the activity and function of the immune system in different ways. In this review, we summarized the main mechanisms of connection between infections, microbiota, immunity, and hormones in autoimmune diseases' onset and progression given the influence of some infections and hormone levels on their pathogenesis. In detail, we focused on rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.
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Affiliation(s)
- Serena Martinelli
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Giulia Nannini
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Fabio Cianchi
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Francesco Coratti
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Amedeo Amedei
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
- SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), 50139 Florence, Italy
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Trier NH, Houen G. Antibody Cross-Reactivity in Auto-Immune Diseases. Int J Mol Sci 2023; 24:13609. [PMID: 37686415 PMCID: PMC10487534 DOI: 10.3390/ijms241713609] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/25/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Autoimmunity is defined by the presence of antibodies and/or T cells directed against self-components. Although of unknown etiology, autoimmunity commonly is associated with environmental factors such as infections, which have been reported to increase the risk of developing autoimmune diseases. Occasionally, similarities between infectious non-self and self-tissue antigens may contribute to immunological cross-reactivity in autoimmune diseases. These reactions may be interpreted as molecular mimicry, which describes cross-reactivity between foreign pathogens and self-antigens that have been reported to cause tissue damage and to contribute to the development of autoimmunity. By focusing on the nature of antibodies, cross-reactivity in general, and antibody-antigen interactions, this review aims to characterize the nature of potential cross-reactive immune reactions between infectious non-self and self-tissue antigens which may be associated with autoimmunity but may not actually be the cause of disease onset.
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Affiliation(s)
- Nicole Hartwig Trier
- Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens Vej 1-23, 2600 Glostrup, Denmark
| | - Gunnar Houen
- Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens Vej 1-23, 2600 Glostrup, Denmark
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
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Nessler JN, Tipold A. Immunoglobulin profiling with large high-density peptide microarrays as screening method to detect candidate proteins for future biomarker detection in dogs with steroid-responsive meningitis-arteritis. PLoS One 2023; 18:e0284010. [PMID: 37036858 PMCID: PMC10085023 DOI: 10.1371/journal.pone.0284010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/22/2023] [Indexed: 04/11/2023] Open
Abstract
Steroid responsive meningitis arteritis (SRMA) is an aberrant Th2-mediated systemic inflammatory disease in dogs. The etiopathogenesis still remains unclear as no triggering pathogen or autoantigen could be found so far. HYPOTHESIS Large high-density peptide microarrays are a suitable screening method to detect possible autoantigens which might be involved in the pathogenesis of SRMA. METHODS The IgA and IgG profile of pooled serum samples of 5 dogs with SRMA and 5 dogs with neck pain due to intervertebral disc herniation (IVDH) without ataxia or paresis were compared via commercially available high-density peptide microarrays (Discovery Microarray) containing 29,240 random linear peptides. Canine distemper virus nucleoprotein (CDVN) served as positive control as all dogs were vaccinated. Common motifs were compared to amino acid sequences of known proteins via databank search. One suitable protein was manually selected for further analysis with a smaller customized high-density peptide microarray. RESULTS Pooled serum of dogs with SRMA and IVDH showed different IgA and IgG responses on Discovery Microarray. Only top IgG responses of dogs with SRMA showed a common motif not related to the control protein CDVN. This common motif is part of the interleukin 1 receptor antagonist protein (IL1Ra). On IL1Ra, dogs with SRMA displayed IgA binding to an additional epitope, which dogs with IVDH did not show. DISCUSSION IL1Ra is an anti-inflammatory acute phase protein. Different immunoglobulin binding patterns on IL1Ra could be involved in the pathogenesis of SRMA and IL1Ra might be developed as future biomarker for SRMA.
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Affiliation(s)
- Jasmin Nicole Nessler
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Foundation, Hannover, Germany
| | - Andrea Tipold
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Foundation, Hannover, Germany
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Al-Khresieh RO, Al-Daghistani HI, Abu-Romman SM, Abu-Niaaj LF. Genetic Signature and Serocompatibility Evidence for Drug Resistant Campylobacter jejuni. Antibiotics (Basel) 2022; 11:1421. [PMID: 36290079 PMCID: PMC9598221 DOI: 10.3390/antibiotics11101421] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/21/2022] Open
Abstract
Campylobacteriosis, a foodborne illness, is one of the world's leading causes of gastrointestinal illness. This study investigates the link between human campylobacteriosis and the consumption of potentially contaminated food with Campylobacter jejuni. Three hundred sixty samples were collected from humans, chicken cloaca, raw chicken meat, unpasteurized milk, and vegetables. The chickens were obtained from licensed and non-licensed slaughterhouses, and only the necks and wings were studied. Samples were enriched under microaerobic conditions then cultured on the modified charcoal cefoperazone deoxycholate agar. Bacteria was identified by staining, biochemical testing, and molecular identification by the polymerase chain reaction for the virulence genes; hipO, asp, dnaJ, cadF, cdtA, cdtB, and cdtC. The genomic homogeneity of C. jejuni between human and chicken isolates was assessed by the serological Penner test and the pulse field gel electrophoresis (PFGE). Campylobacter was not detected in the vegetables and pasteurized milk, though, only twenty isolates from chickens and clinical samples were presumed to be Campylobacter based on their morphology. The biochemical tests confirmed that five isolates were C. coli, and fifteen isolates were C. jejuni including two isolates from humans, and the remaining were from chickens. The colonization of C. jejuni in chickens was significantly lower in necks (6.66%) obtained from licensed slaughterhouses compared to those obtained from non-licensed slaughterhouses (33.3%). The antimicrobial susceptibility test showed that all identified C. jejuni isolates were resistant to antibiotics, and the majority of isolates (53.5%) showed resistance against six antibiotics, though, all isolates were resistant to ciprofloxacin, tetracycline, and aztreonam. The Penner test showed P:21 as the dominant serotype in isolates from humans, necks, and cloaca. The serohomology of C. jejuni from human isolates and chicken necks, wings, and cloaca was 71%, 36%, 78%, respectively. The PFGE analysis of the pattern for DNA fragmentation by the restriction enzyme Smal showed a complete genotypic homology of C. jejuni human isolates and chicken necks compared to partial homology with cloacal isolates. The study brings attention to the need for effective interventions to ensure best practices for safe poultry production for commercial food chain supply to limit infection with foodborne pathogens, including Campylobacter.
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Affiliation(s)
- Rozan O. Al-Khresieh
- Department of Medical Laboratory Sciences, Faculty of Sciences, Al-Balqa Applied University, Al-Salt 19117, Jordan
| | - Hala I. Al-Daghistani
- Department of Medical Laboratory Sciences, Faculty of Medical Allied Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Saeid M. Abu-Romman
- Department of Biotechnology, Faculty of Agricultural Technology, Al-Balqa Applied University, Al-Salt 19117, Jordan
| | - Lubna F. Abu-Niaaj
- Department of Agricultural and Life Sciences, John W. Garland College of Engineering, Science, Technology and Agriculture, Central State University, Wilberforce, OH 45384, USA
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Stein RA. Campylobacter jejuni and Postinfectious Autoimmune Diseases: A Proof of Concept in Glycobiology. ACS Infect Dis 2022; 8:1981-1991. [PMID: 36137262 DOI: 10.1021/acsinfecdis.2c00397] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Glycans, one of the most diverse groups of macromolecules, are ubiquitous constituents of all cells and have many critical functions, including the interaction between microbes and their hosts. One of the best model organisms to study the host-pathogen interaction, the gastrointestinal pathogen Campylobacter jejuni dedicates extensive resources to glycosylation and exhibits a diverse array of surface sugar-coated displays. The first bacterium where N-linked glycosylation was described, C. jejuni can additionally modify proteins by O-linked glycosylation, has extracellular capsular polysaccharides that are important for virulence and represent the major determinant of the Penner serotyping scheme, and has outer membrane lipooligosaccharides that participate in processes such as colonization, survival, inflammation, and immune evasion. In addition to causing gastrointestinal disease and extraintestinal infections, C. jejuni was also linked to postinfectious autoimmune neuropathies, of which Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are the most extensively characterized ones. These postinfectious autoimmune neuropathies occur when specific bacterial surface lipooligosaccharides mimic gangliosides in the host nervous system. C. jejuni provided the first proof of concept for the involvement of molecular mimicry in the pathogenesis of an autoimmune disease and, also, for the ability of a bacterial polymorphism to shape the clinical presentation of the postinfectious autoimmune neuropathy. The scientific journey that culminated with elucidating the mechanistic details of the C. jejuni-GBS link was the result of contributions from several fields, including microbiology, structural biology, glycobiology, genetics, and immunology and provides an inspiring and important example to interrogate other instances of molecular mimicry and their involvement in autoimmune disease.
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Affiliation(s)
- Richard A Stein
- Industry Associate Professor NYU Tandon School of Engineering, Department of Chemical and Biomolecular Engineering, 6 MetroTech Center, Brooklyn, New York 11201, United States
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Rizzi L, Sabbà C, Suppressa P. Sarcoidosis and autoimmunity: In the depth of a complex relationship. Front Med (Lausanne) 2022; 9:991394. [PMID: 36148452 PMCID: PMC9485866 DOI: 10.3389/fmed.2022.991394] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 08/01/2022] [Indexed: 11/25/2022] Open
Abstract
Sarcoidosis is a chronic granulomatous disease that can virtually affect any organ. Its etiology is unknown, although it has been proposed that environmental or biological agents can act as triggers, ultimately leading to chronic inflammation in genetically predisposed individuals. The main component of sarcoid inflammation is represented by an exaggerated T- lymphocytic cellular response to a putative antigen that could not be efficiently cleared in the patient. However, several clinical and immunological observations, such as the association of sarcoidosis to autoimmune diseases or the presence of autoantibodies in the serum of patients with sarcoidosis, suggest that humoral-mediated immune response might also play a role in the pathogenesis of sarcoidosis. The aim of this review is to deepen the relationship between sarcoidosis and autoimmunity, by analyzing the most recent advances and proposing new fields of research.
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Sharma S, Adhikari A, Ghimire N, Mainali G, Yadav SK, Rajkarnikar R. Guillain-Barré Syndrome associated with SARS-CoV-2 infection in Nepal: A case report. Ann Med Surg (Lond) 2022; 80:104214. [PMID: 35936572 PMCID: PMC9339100 DOI: 10.1016/j.amsu.2022.104214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 07/14/2022] [Accepted: 07/20/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction Corona viruses may also affect the central nervous system, inducing various neurological problems. Guillain-Barré Syndrome (GBS) is a rare immune-mediated post-infectious neuropathy typically leading to ascending weakness. Herein, we present a case of the patient to show an association of GBS and SARS-CoV-2 infection in Nepal Case presentation Twenty-seven yrs old man show an association of GBS and SARS-CoV-2 infection in Nepal who presented with difficulty in walking, backache, tingling sensations over the bilateral wrist and ankle, and features of facial nerve palsy. The diagnosis of GBS was made. Following Intravenous Immunoglobulin (IVIg) administration, the patient started showing motor recovery within a week. Clinical discussion Patient who developed GBS as a likely post-infectious complication after the initial onset of infectious symptoms with persistent mild dry cough. Conclusion GBS has severe complications and early diagnosis is important to monitor for loss of ambulation and initiation of immunoglobulin treatment. GBS should be considered as a potential rare but serious complication due to COVID-19
Corona viruses may also affect the central nervous system, inducing various neurological problems. GBS is a rare immune-mediated post-infectious neuropathy typically leading to ascending weakness. There is association od GBS and SARS-CoV-2 infection. GBS should be considered as a potential rare but serious complication due to COVID-19.
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13
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Gershteyn IM, Burov AA, Miao BY, Morais VH, Ferreira LMR. Immunodietica: interrogating the role of diet in autoimmune disease. Int Immunol 2021; 32:771-783. [PMID: 32808986 DOI: 10.1093/intimm/dxaa054] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/10/2020] [Indexed: 12/12/2022] Open
Abstract
Diet is an environmental factor in autoimmune disorders, where the immune system erroneously destroys one's own tissues. Yet, interactions between diet and autoimmunity remain largely unexplored, particularly the impact of immunogenetics, one's human leukocyte antigen (HLA) allele make-up, in this interplay. Here, we interrogated animals and plants for the presence of epitopes implicated in human autoimmune diseases. We mapped autoimmune epitope distribution across organisms and determined their tissue expression pattern. Interestingly, diet-derived epitopes implicated in a disease were more likely to bind to HLA alleles associated with that disease than to protective alleles, with visible differences between organisms with similar autoimmune epitope content. We then analyzed an individual's HLA haplotype, generating a personalized heatmap of potential dietary autoimmune triggers. Our work uncovered differences in autoimmunogenic potential across food sources and revealed differential binding of diet-derived epitopes to autoimmune disease-associated HLA alleles, shedding light on the impact of diet on autoimmunity.
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Affiliation(s)
- Iosif M Gershteyn
- Ajax Biomedical Foundation, Newton, MA, USA
- ImmuVia LLC, Waltham, MA, USA
- SoundMedicine LLC, Waltham, MA, USA
| | | | - Brenda Y Miao
- Diabetes Center, University of California, San Francisco, San Francisco, CA, USA
| | - Vasco H Morais
- Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Leonardo M R Ferreira
- Ajax Biomedical Foundation, Newton, MA, USA
- Diabetes Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
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14
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Armijos-Jaramillo V, Espinosa N, Vizcaíno K, Santander-Gordón D. A Novel In Silico Method for Molecular Mimicry Detection Finds a Formin with the Potential to Manipulate the Maize Cell Cytoskeleton. MOLECULAR PLANT-MICROBE INTERACTIONS : MPMI 2021; 34:815-825. [PMID: 33755496 DOI: 10.1094/mpmi-11-20-0332-r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Molecular mimicry is one of the evolutionary strategies that parasites use to manipulate the host metabolism and perform an effective infection. This phenomenon has been observed in several animal and plant pathosystems. Despite the relevance of this mechanism in pathogenesis, little is known about it in fungus-plant interactions. For that reason, we performed an in silico method to select plausible mimicry candidates for the Ustilago maydis-maize interaction. Our methodology used a tripartite sequence comparison between the parasite, the host, and nonparasitic organisms' genomes. Furthermore, we used RNA sequencing information to identify gene coexpression, and we determined subcellular localization to detect potential cases of colocalization in the imitator-imitated pairs. With these approximations, we found a putative extracellular formin in U. maydis with the potential to rearrange the host cell cytoskeleton. In parallel, we detected at least two maize genes involved in the cytoskeleton rearrangement differentially expressed under U. maydis infection; thus, this find increases the expectation for the potential mimicry role of the fungal protein. The use of several sources of data led us to develop a strict and replicable in silico methodology to detect molecular mimicry in pathosystems with enough information available. Furthermore, this is the first time that a genomewide search has been performed to detect molecular mimicry in a U. maydis-maize system. Additionally, to allow the reproducibility of this experiment and the use of this pipeline, we created a Web server called Molecular Mimicry Finder.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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Affiliation(s)
- Vinicio Armijos-Jaramillo
- Carrera de Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito, Ecuador
- Grupo de Bio-Quimioinformática, Universidad de Las Américas, Quito, Ecuador
| | - Nicole Espinosa
- Carrera de Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito, Ecuador
| | - Karla Vizcaíno
- Carrera de Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito, Ecuador
| | - Daniela Santander-Gordón
- Carrera de Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Américas, Quito, Ecuador
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15
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Shahrizaila N, Lehmann HC, Kuwabara S. Guillain-Barré syndrome. Lancet 2021; 397:1214-1228. [PMID: 33647239 DOI: 10.1016/s0140-6736(21)00517-1] [Citation(s) in RCA: 333] [Impact Index Per Article: 83.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 05/07/2020] [Accepted: 08/28/2020] [Indexed: 12/11/2022]
Abstract
Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.
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Affiliation(s)
- Nortina Shahrizaila
- Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
| | - Helmar C Lehmann
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Satoshi Kuwabara
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
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16
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Low-Dose Exposure to Ganglioside-Mimicking Bacteria Tolerizes Human Macrophages to Guillain-Barré Syndrome-Associated Antigens. mBio 2021; 13:e0385221. [PMID: 35100875 PMCID: PMC8805021 DOI: 10.1128/mbio.03852-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Early in life, commensal bacteria play a major role in immune development, helping to guide the host response toward harmful stimuli while tolerating harmless antigens to prevent autoimmunity. Guillain-Barré syndrome (GBS) is an autoimmune disease caused by errant immune attack of antibody-bound ganglioside receptors on host nerve cells, resulting in paralysis. Lipooligosaccharides enveloping the prevalent enteric pathogen, Campylobacter jejuni, frequently mimic human gangliosides and can trigger GBS by stimulating the autoimmune response. In low- to middle-income countries, young children are consistently exposed to C. jejuni, and it is not known if this impacts GBS susceptibility later in life. Using a macrophage model, we examined the effect of training these cells with low doses of ganglioside-mimicking bacteria prior to challenge with GBS-associated antigens. This training caused decreased production of proinflammatory cytokines, suggesting tolerance induction. We then screened Campylobacter isolates from 154 infant fecal samples for GM1 ganglioside mimicry, finding that 23.4% of strains from both symptomatic and asymptomatic infants displayed GM1-like structures. Training macrophages with one of these asymptomatic carrier isolates also induced tolerance against GBS-associated antigens, supporting that children can be exposed to the tolerizing antigen early in life. RNA interference of Toll-like receptor 2 (TLR2) and TLR4 suggests that these receptors are not involved in tolerance associated with decreases in tumor necrosis factor (TNF), interleukin-6 (IL-6), or IL-1β levels. The results of this study suggest that exposure to ganglioside-mimicking bacteria early in life occurs naturally and impacts host susceptibility to GBS development. IMPORTANCE In this study, we demonstrated that it is possible to tolerize immune cells to potentially dampen the autoreactive proinflammatory immune response against Guillain-Barré syndrome (GBS)-associated antigens. The innate immune response functions to arm the host against bacterial attack, but it can be tricked into recognizing the host's own cells when infectious bacteria display sugar structures that mimic human glycans. It is this errant response that leads to the autoimmunity and paralysis associated with GBS. By presenting immune cells with small amounts of the bacterial glycan mimic, we were able to suppress the proinflammatory immune response upon subsequent high exposure to glycan-mimicking bacteria. This suggests that individuals who have already been exposed to the glycan mimics in small amounts are less sensitive to autoimmune reactions against these glycans, and this could be a factor in determining susceptibility to GBS.
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17
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Rajabally YA, Attarian S, Delmont E. Evolving Immunologic Perspectives in Chronic Inflammatory Demyelinating Polyneuropathy. J Inflamm Res 2020; 13:543-549. [PMID: 32982369 PMCID: PMC7502403 DOI: 10.2147/jir.s224781] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/26/2020] [Indexed: 12/17/2022] Open
Abstract
Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest chronic idiopathic dysimmune neuropathy. Pathophysiologic processes involve both cellular and humoral immunity. There are various known forms of CIDP, likely caused by varying mechanisms. CIDP in its different forms is a treatable disorder in the majority of patients. The diagnosis of CIDP is clinical, supported routinely by electrophysiology. Cerebrospinal fluid analysis may be helpful. Routine immunology currently rarely adds to the diagnostic process but may contribute to the identification of an associated monoclonal gammopathy with or without hematologic malignancy and the consideration of alternative diagnoses, such as POEMS syndrome, anti-myelin associated glycoprotein (MAG) neuropathy or chronic ataxic neuropathy, with ophthalmoplegia, M-protein, cold aglutinins and disialosyl antibodies (CANOMAD). The search for antibodies specific to CIDP has been unsuccessful for many years. Recently, antibodies to paranodal proteins have been identified in a minority of patients with severe CIDP phenotypes, often unresponsive to first-line therapies. In conjunction with reports of high rates of antibody responses to neural structures in CIDP, this entertains the hope that more discoveries are to come. Although still arguably for only a small minority of patients, in view of current knowledge, such progress will enable earlier accurate diagnosis with direct management implications but only if the important, unfortunately and infrequently discussed issues of immunologic technique, test reliability and reproducibility are adequately tackled.
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Affiliation(s)
- Yusuf A Rajabally
- Inflammatory Neuropathy Clinic, University Hospitals Birmingham, Birmingham, UK.,Aston Medical School, Aston University, Birmingham, UK
| | - Shahram Attarian
- Reference Centre for Neuromuscular Diseases and ALS, Centre Hospitalier Universitaire La Timone, Marseille 13385, France.,Aix-Marseille University, Inserm, GMGF, Marseille, France
| | - Emilien Delmont
- Reference Centre for Neuromuscular Diseases and ALS, Centre Hospitalier Universitaire La Timone, Marseille 13385, France.,Aix-Marseille University, Inserm, GMGF, Marseille, France
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18
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Khalifa M, Zakaria F, Ragab Y, Saad A, Bamaga A, Emad Y, Rasker JJ. Guillain-Barré Syndrome Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Detection and Coronavirus Disease 2019 in a Child. J Pediatric Infect Dis Soc 2020; 9:510-513. [PMID: 32652520 PMCID: PMC7454732 DOI: 10.1093/jpids/piaa086] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/08/2020] [Indexed: 12/29/2022]
Abstract
Coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Physicians in China reported what is believed to be the first adult case of a SARS-CoV-2 infection associated with acute Guillain-Barré syndrome (GBS), followed by 5 adult Italian patients and another case in the United States. In the current report, we present one of the first descriptions of an association of GBS and SARS-CoV-2 infection in a child. In our facility, an 11-year-old boy presented with typical features of GBS and, after 5 days, a morbilliform skin rash over the palms of both hands. Three weeks before the start of the neurological symptoms, the boy had experienced an episode of mild febrile illness with mild respiratory manifestations and a persistent cough. The diagnosis of SARS-CoV-2 infection was confirmed by oropharyngeal swab on reverse-transcription polymerase chain reaction assay. The disease course of our patient strongly suggests a possible relationship between the development of GBS and SARS-CoV-2 infection. The case is discussed in view of previous case reports regarding the association of GBS and COVID-19.
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Affiliation(s)
- Maher Khalifa
- Pediatric Neurology Department, Dr Erfan and Bagedo General Hospital, Jeddah, Kingdom of Saudi Arabia
| | - Fairouz Zakaria
- Pediatric Neurology Department, Dr Erfan and Bagedo General Hospital, Jeddah, Kingdom of Saudi Arabia
| | - Yasser Ragab
- Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Saad
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Bamaga
- Pediatric Department, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia
| | - Yasser Emad
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Johannes J Rasker
- Faculty of Behavioral, Management and Social Sciences, Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands,Correspondence: Maher Khalifa, FRCP, FRCPCH, Pediatric Neurology Department, Dr Erfan and Bagedo General Hospital, Jeddah, Kingdom of Saudi Arabia. E-mail:
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19
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Kumar V. Innate lymphoid cell and adaptive immune cell cross-talk: A talk meant not to forget. J Leukoc Biol 2020; 108:397-417. [PMID: 32557732 DOI: 10.1002/jlb.4mir0420-500rrr] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 04/28/2020] [Accepted: 05/04/2020] [Indexed: 12/17/2022] Open
Abstract
Innate lymphoid cells (ILCs) are a relatively new class of innate immune cells with phenotypical characters of lymphocytes but genotypically or functionally behave as typical innate immune cells. They have been classically divided into 3 groups (group 1 ILCs or ILC1s, group 2 ILCs or ILC2s, and group 3 ILCs or ILC3s). They serve as the first line of defense against invading pathogens and allergens at mucosal surfaces. The adaptive immune response works effectively in association with innate immunity as innate immune cells serve as APCs to directly stimulate the adaptive immune cells (various sets of T and B cells). Additionally, innate immune cells also secrete various effector molecules, including cytokines or chemokines impacting the function, differentiation, proliferation, and reprogramming among adaptive immune cells to maintain immune homeostasis. Only superantigens do not require their processing by innate immune cells as they are recognized directly by T cells and B cells. Thus, a major emphasis of the current article is to describe the cross-talk between different ILCs and adaptive immune cells during different conditions varying from normal physiological situations to different infectious diseases to allergic asthma.
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Affiliation(s)
- V Kumar
- Children's Health Queensland Clinical Unit, School of Clinical Medicine, Faculty of Medicine, Mater Research, University of Queensland, Brisbane, Queensland, Australia.,School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
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20
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A Journey to the Conformational Analysis of T-Cell Epitope Peptides Involved in Multiple Sclerosis. Brain Sci 2020; 10:brainsci10060356. [PMID: 32521758 PMCID: PMC7349157 DOI: 10.3390/brainsci10060356] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/01/2020] [Accepted: 06/02/2020] [Indexed: 01/22/2023] Open
Abstract
Multiple sclerosis (MS) is a serious central nervous system (CNS) disease responsible for disability problems and deterioration of the quality of life. Several approaches have been applied to medications entering the market to treat this disease. However, no effective therapy currently exists, and the available drugs simply ameliorate the destructive disability effects of the disease. In this review article, we report on the efforts that have been conducted towards establishing the conformational properties of wild-type myelin basic protein (MBP), myelin proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG) epitopes or altered peptide ligands (ALPs). These efforts have led to the aim of discovering some non-peptide mimetics possessing considerable activity against the disease. These efforts have contributed also to unveiling the molecular basis of the molecular interactions implicated in the trimolecular complex, T-cell receptor (TCR)–peptide–major histocompatibility complex (MHC) or human leucocyte antigen (HLA).
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21
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Shin YW, Lee ST, Kim YS, Han D, Nogi Y, Chu K, Lee SK. Distinct immunoreactivity pattern to Bacillus mannanilyticus in a subgroup of anti-NMDA receptor encephalitis. J Neuroimmunol 2020; 342:577215. [PMID: 32182453 DOI: 10.1016/j.jneuroim.2020.577215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 03/08/2020] [Accepted: 03/11/2020] [Indexed: 10/24/2022]
Abstract
Over half of anti-NMDA receptor encephalitis (NMDARE) is unrelated to etiologies such as teratomas or herpes simplex encephalitis. Bacillus mannanilyticus nonribosomal peptide synthetase (NRPS) shares a protein sequence with GluN1. After confirming the anti-NRPS antibody immunoreactivity in an index patient by liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 24/57 (42%) patients with similar immunoreactivity patterns by western blotting. These patients mostly (20/24 [83%]) did not have ovarian teratomas, had fewer medial temporal (2/24 [8%]) and any (5/24 [21%]) brain lesions and less pleocytosis (13/24 [54%]). These results identified an anti-NMDARE subgroup with a distinct immunoreactivity pattern, which needs further investigation.
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Affiliation(s)
- Yong-Won Shin
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul, South Korea
| | - Soon-Tae Lee
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
| | - Young-Sook Kim
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea
| | - Dohyun Han
- Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
| | - Yuichi Nogi
- Extremobiosphere Research Center, Japan Agency for Marine-Earth Science and Technology, Yokosuka, Japan
| | - Kon Chu
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea
| | - Sang Kun Lee
- Department of Neurology, Seoul National University Hospital, Seoul, South Korea
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22
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Vojdani A, Gushgari LR, Vojdani E. Interaction between food antigens and the immune system: Association with autoimmune disorders. Autoimmun Rev 2020; 19:102459. [PMID: 31917265 DOI: 10.1016/j.autrev.2020.102459] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 08/19/2019] [Indexed: 02/08/2023]
Abstract
It has been shown that environmental factors such as infections, chemicals, and diet play a major role in autoimmune diseases; however, relatively little attention has been given to food components as the most prevalent modifiers of these afflictions. This review summarizes the current body of knowledge related to different mechanisms and associations between food proteins/peptides and autoimmune disorders. The primary factor controlling food-related immune reactions is the oral tolerance mechanism. The failure of oral tolerance triggers immune reactivity against dietary antigens, which may initiate or exacerbate autoimmune disease when the food antigen shares homology with human tissue antigens. Because the conformational fit between food antigens and a host's self-determinants has been determined for only a few food proteins, we examined evidence related to the reaction of affinity-purified disease-specific antibody with different food antigens. We also studied the reaction of monoclonal or polyclonal tissue-specific antibodies with various food antigens and the reaction of food-specific antibodies with human tissue antigens. Examining the assembled information, we postulated that chemical modification of food proteins by different toxicants in food may result in immune reaction against modified food proteins that cross-react with tissue antigens, resulting in autoimmune reactivity. Because we are what our microbiome eats, food can change the gut commensals, and toxins can breach the gut barrier, penetrating into different organs where they can initiate autoimmune response. Conversely, there are also foods and supplements that help maintain oral tolerance and microbiome homeostasis. Understanding the potential link between specific food consumption and autoimmunity in humans may lay the foundation for further research about the proper diet in the prevention of autoimmune diseases.
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Affiliation(s)
- Aristo Vojdani
- Immunosciences Lab, Inc., 822 S. Robertson Blvd, Ste. 312, Los Angeles, CA 90035, USA; Department of Preventive Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
| | - Lydia R Gushgari
- Cyrex Laboratories, LLC. 2602 South 24(th) St., Phoenix, AZ 85034, USA.
| | - Elroy Vojdani
- Regenera Medical, 11860 Wilshire Blvd., Ste. 301, Los Angeles, CA 90025, USA.
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23
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Zhang G, Wang Q, Song Y, Cheng P, Xu R, Feng X, Li X. Intravenous immunoglobulin promotes the proliferation of CD4 +CD25 + Foxp3 + regulatory T cells and the cytokines secretion in patients with Guillain-Barré syndrome in vitro. J Neuroimmunol 2019; 336:577042. [PMID: 31479869 DOI: 10.1016/j.jneuroim.2019.577042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 08/24/2019] [Accepted: 08/26/2019] [Indexed: 10/26/2022]
Abstract
Intravenous immunoglobulin (IVIg) serves as the first line therapy in Guillain-Barré syndrome (GBS), however, its action mechanism remains unknown. We hereby stimulated peripheral blood mononuclear cells (PBMCs) from patients with GBS and healthy controls using IVIg and an IgG-derived natural Treg epitopes, namely Tregitopes. Our results showed that IVIg significantly promoted both the expansion of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and secretion of IL-10 and TGF-β1 while Tregitopes promoted secretion of IL-10 and TGF-β1 only. Further study is necessary to elucidate the molecular mechanism of IVIg and Tregitopes on Tregs and the secretion of IL-10 and TGF-β1 in GBS.
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Affiliation(s)
- Guorong Zhang
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Quanquan Wang
- Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Yan Song
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Panpan Cheng
- Department of Haemotology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Ranran Xu
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Xungang Feng
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Xiang Li
- Department of rehabilitation, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.
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24
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Gershteyn IM, Ferreira LMR. Immunodietica: A data-driven approach to investigate interactions between diet and autoimmune disorders. J Transl Autoimmun 2019; 1:100003. [PMID: 32743493 PMCID: PMC7388395 DOI: 10.1016/j.jtauto.2019.100003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 05/17/2019] [Accepted: 05/19/2019] [Indexed: 12/30/2022] Open
Abstract
Autoimmunity is on the rise around the globe. Diet has been proposed as a risk factor for autoimmunity and shown to modulate the severity of several autoimmune disorders. Yet, the interaction between diet and autoimmunity in humans remains largely unstudied. Here, we systematically interrogated commonly consumed animals and plants for peptide epitopes previously implicated in human autoimmune disease. A total of fourteen species investigated could be divided into three broad categories regarding their content in human autoimmune epitopes, which we represented using a new metric, the Gershteyn-Ferreira index (GF index). Strikingly, pig contains a disproportionately high number of unique autoimmune epitopes compared to all other species analyzed. This work uncovers a potential new link between pork consumption and autoimmunity in humans and lays the foundation for future studies on the impact of diet on the pathogenesis and progression of autoimmune disorders.
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Affiliation(s)
- Iosif M Gershteyn
- Ajax Biomedical Foundation, Newton, MA, United States.,ImmuVia LLC, Waltham, MA, United States
| | - Leonardo M R Ferreira
- Ajax Biomedical Foundation, Newton, MA, United States.,Department of Surgery, Transplantation Research Laboratory, University of California San Francisco, San Francisco, CA, United States.,Diabetes Center, Sean N. Parker Autoimmunity Research Laboratory, University of California San Francisco, San Francisco, CA, United States
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25
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Patry RT, Stahl M, Perez-Munoz ME, Nothaft H, Wenzel CQ, Sacher JC, Coros C, Walter J, Vallance BA, Szymanski CM. Bacterial AB 5 toxins inhibit the growth of gut bacteria by targeting ganglioside-like glycoconjugates. Nat Commun 2019; 10:1390. [PMID: 30918252 PMCID: PMC6437147 DOI: 10.1038/s41467-019-09362-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 03/05/2019] [Indexed: 12/21/2022] Open
Abstract
The AB5 toxins cholera toxin (CT) from Vibrio cholerae and heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli are notorious for their roles in diarrheal disease, but their effect on other intestinal bacteria remains unexplored. Another foodborne pathogen, Campylobacter jejuni, can mimic the GM1 ganglioside receptor of CT and LT. Here we demonstrate that the toxin B-subunits (CTB and LTB) inhibit C. jejuni growth by binding to GM1-mimicking lipooligosaccharides and increasing permeability of the cell membrane. Furthermore, incubation of CTB or LTB with a C. jejuni isolate capable of altering its lipooligosaccharide structure selects for variants lacking the GM1 mimic. Examining the chicken GI tract with immunofluorescence microscopy demonstrates that GM1 reactive structures are abundant on epithelial cells and commensal bacteria, further emphasizing the relevance of this mimicry. Exposure of chickens to CTB or LTB causes shifts in the gut microbial composition, providing evidence for new toxin functions in bacterial gut competition. Bacterial AB5 toxins, such as cholera toxin, bind to oligosaccharides on the host cell surface and play key roles in the pathogenesis of diarrheal disease. Here, Patry et al. show that these toxins bind also to bacterial oligosaccharides and inhibit the growth of Campylobacter jejuni and gut commensal bacteria.
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Affiliation(s)
- Robert T Patry
- Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA.,Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| | - Martin Stahl
- Division of Gastroenterology, BC Children's Hospital Research Institute, The University of British Columbia, Vancouver, BC, V6H 3V4, Canada
| | - Maria Elisa Perez-Munoz
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Harald Nothaft
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| | - Cory Q Wenzel
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| | - Jessica C Sacher
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada
| | - Colin Coros
- Delta Genomics, Edmonton, AB, T5J 4P6, Canada
| | - Jens Walter
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada.,Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Bruce A Vallance
- Division of Gastroenterology, BC Children's Hospital Research Institute, The University of British Columbia, Vancouver, BC, V6H 3V4, Canada
| | - Christine M Szymanski
- Department of Microbiology and Complex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA. .,Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada.
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Antibody specificity and promiscuity. Biochem J 2019; 476:433-447. [PMID: 30723137 DOI: 10.1042/bcj20180670] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 01/06/2019] [Accepted: 01/07/2019] [Indexed: 12/16/2022]
Abstract
The immune system is capable of making antibodies against anything that is foreign, yet it does not react against components of self. In that sense, a fundamental requirement of the body's immune defense is specificity. Remarkably, this ability to specifically attack foreign antigens is directed even against antigens that have not been encountered a priori by the immune system. The specificity of an antibody for the foreign antigen evolves through an iterative process of somatic mutations followed by selection. There is, however, accumulating evidence that the antibodies are often functionally promiscuous or multi-specific which can lead to their binding to more than one antigen. An important cause of antibody cross-reactivity is molecular mimicry. Molecular mimicry has been implicated in the generation of autoimmune response. When foreign antigen shares similarity with the component of self, the antibodies generated could result in an autoimmune response. The focus of this review is to capture the contrast between specificity and promiscuity and the structural mechanisms employed by the antibodies to accomplish promiscuity, at the molecular level. The conundrum between the specificity of the immune system for foreign antigens on the one hand and the multi-reactivity of the antibody on the other has been addressed. Antibody specificity in the context of the rapid evolution of the antigenic determinants and molecular mimicry displayed by antigens are also discussed.
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Abstract
Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues to target the microbiota for the clinical management of AAU and SpA are outlined.
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Affiliation(s)
- James T Rosenbaum
- Departments of Ophthalmology, Medicine and Cell Biology, Oregon Health and Science University, Portland, OR, USA
- Legacy Devers Eye Institute, Portland, OR, USA
| | - Mark Asquith
- Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
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Rojas M, Restrepo-Jiménez P, Monsalve DM, Pacheco Y, Acosta-Ampudia Y, Ramírez-Santana C, Leung PS, Ansari AA, Gershwin ME, Anaya JM. Molecular mimicry and autoimmunity. J Autoimmun 2018; 95:100-123. [DOI: 10.1016/j.jaut.2018.10.012] [Citation(s) in RCA: 214] [Impact Index Per Article: 30.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/12/2018] [Accepted: 10/16/2018] [Indexed: 12/15/2022]
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Tzoupis H, Tselios T. In Silico Drug Design: Non-peptide Mimetics for the Immunotherapy of Multiple Sclerosis. Methods Mol Biol 2018; 1824:33-47. [PMID: 30039400 DOI: 10.1007/978-1-4939-8630-9_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Advances in theoretical chemistry have led to the development of various robust computational techniques employed in drug design. Pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulations have been extensively applied, separately or in combination, in the design of potent molecules. The techniques involve the identification of a potential drug target (e.g., protein) and its subsequent characterization. The next step in the process comprises the development of a map describing the interaction patterns between the target molecule and its natural substrate. Once these key features are identified, it is possible to explore the map and screen large databases of molecules to identify potential drug candidates for further refinement.Multiple sclerosis (MS) is an autoimmune disease where the immune system attacks the myelin sheath of nerve cells. The process involves the activation of encephalitogenic T cells via the formation of the trimolecular complex between the human leukocyte antigen (HLA), an immunodominant epitope of myelin proteins, and the T-cell receptor (TCR). Herein, the process for rational design and development of altered peptide ligands (APLs) and non-peptide mimetics against MS is described through the utilization of computational methods.
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Tapeinou A, Giannopoulou E, Simal C, Hansen BE, Kalofonos H, Apostolopoulos V, Vlamis-Gardikas A, Tselios T. Design, synthesis and evaluation of an anthraquinone derivative conjugated to myelin basic protein immunodominant (MBP 85-99) epitope: Towards selective immunosuppression. Eur J Med Chem 2017; 143:621-631. [PMID: 29216561 DOI: 10.1016/j.ejmech.2017.11.063] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/14/2017] [Accepted: 11/22/2017] [Indexed: 02/09/2023]
Abstract
Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described. The compound consists of the myelin basic protein (MBP) 85-99 immunodominant epitope (MBP85-99) coupled to an anthraquinone type molecule (AQ) via a disulfide (S-S) and 6 amino hexanoic acid (Ahx) residues (AQ-S-S-(Ahx)6MBP85-99). AQ-S-S-(Ahx)6MBP85-99 could bind to HLA II DRB1*-1501 antigen with reasonable affinity (IC50 of 56 nM) The compound was localized to the nucleus of Jurkat cells (an immortalized line of human T lymphocytes) 10 min after its addition to the medium and resulted in lowered Bcl-2 levels (apoptosis). Entrance of the compound was abolished when cells were pre-treated with cisplatin, an inhibitor of thioredoxin reductase. Accordingly, levels of free thiols were elevated in the culture supernatants of Jurkat cells exposed to N-succinimidyl 3-(2-pyridyldithio) propionate coupled to (Ahx)6MBP85-99 via a disulphide (SPDP-S-S-(Ahx)6MBP85-99) but returned to normal after exposure to cisplatin. These results raise the possibility of AQ-S-S-(Ahx)6MBP85-99 being used as an eliminator of encephalitogenic T cells via implication of the thioredoxin system for the generation of the toxic, thiol-containing moiety (AQ-SH). Future experiments would ideally determine whether SPDP-S-S-(Ahx)6MBP85-99 could incorporate into HLA II DRB1*-1501 tetramers and neutralize encephalitogenic T cell lines sensitized to MBP85-99.
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Affiliation(s)
- Anthi Tapeinou
- Department of Chemistry, University of Patras, GR-26504, Rion, Greece
| | - Efstathia Giannopoulou
- Clinical Oncology Laboratory, University Hospital of Patras, Patras Medical School, GR-26504, Rion, Greece
| | - Carmen Simal
- Department of Chemistry, University of Patras, GR-26504, Rion, Greece
| | - Bjarke E Hansen
- Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
| | - Haralabos Kalofonos
- Clinical Oncology Laboratory, University Hospital of Patras, Patras Medical School, GR-26504, Rion, Greece
| | - Vasso Apostolopoulos
- Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia
| | | | - Theodore Tselios
- Department of Chemistry, University of Patras, GR-26504, Rion, Greece.
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Bulbar paralysis associated with Miller-Fisher syndrome and its overlaps in Chinese patients. Neurol Sci 2017; 39:305-311. [DOI: 10.1007/s10072-017-3184-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 11/01/2017] [Indexed: 11/25/2022]
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Kordopati GG, Tzoupis H, Troganis AN, Tsivgoulis GM, Golic Grdadolnik S, Simal C, Tselios TV. Biologically relevant conformational features of linear and cyclic proteolipid protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic resonance and molecular dynamics. J Comput Aided Mol Des 2017; 31:841-854. [PMID: 28756481 DOI: 10.1007/s10822-017-0045-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 07/26/2017] [Indexed: 11/24/2022]
Abstract
Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L144, R147) PLP139-151, have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations. The results indicate that the side chains of mutated amino acids in the cyclic analogue have different spatial orientation compared with the corresponding side chains of the linear analogue, which can lead to reduced affinity to TCR. NMR experiments combined with theoretical calculations pave the way for the design and synthesis of potent restricted peptides of immunodominant PLP139-151 epitope as well as non peptide mimetics that rises as an ultimate goal.
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Affiliation(s)
- Golfo G Kordopati
- Department of Chemistry, University of Patras, 26504, Patras, Greece
| | | | - Anastassios N Troganis
- Department of Biological Applications and Technology, University of Ioannina, 45110, Ioannina, Greece
| | | | - Simona Golic Grdadolnik
- Department of Biomolecular Structure, National Institute of Chemistry, 1001, Ljubljana, Slovenia
| | - Carmen Simal
- Department of Chemistry, University of Patras, 26504, Patras, Greece
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Chmiela M, Gonciarz W. Molecular mimicry in Helicobacter pylori infections. World J Gastroenterol 2017; 23:3964-3977. [PMID: 28652651 PMCID: PMC5473117 DOI: 10.3748/wjg.v23.i22.3964] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 05/26/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.
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Design and Synthesis of Non-Peptide Mimetics Mapping the Immunodominant Myelin Basic Protein (MBP 83-96) Epitope to Function as T-Cell Receptor Antagonists. Int J Mol Sci 2017; 18:ijms18061215. [PMID: 28594344 PMCID: PMC5486038 DOI: 10.3390/ijms18061215] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 06/02/2017] [Accepted: 06/02/2017] [Indexed: 01/08/2023] Open
Abstract
Encephalitogenic T cells are heavily implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Their stimulation is triggered by the formation of a trimolecular complex between the human leukocyte antigen (HLA), an immunodominant myelin basic protein (MBP) epitope, and the T cell receptor (TCR). We detail herein our studies directed towards the rational design and synthesis of non-peptide mimetic molecules, based on the immunodominant MBP83-96 epitope that is recognized by the TCR in complex with HLA. We focused our attention on the inhibition of the trimolecular complex formation and consequently the inhibition of proliferation of activated T cells. A structure-based pharmacophore model was generated, in view of the interactions between the TCR and the HLA-MBP83-96 complex. As a result, new candidate molecules were designed based on lead compounds obtained through the ZINC database. Moreover, semi-empirical and density functional theory methods were applied for the prediction of the binding energy between the proposed non-peptide mimetics and the TCR. We synthesized six molecules that were further evaluated in vitro as TCR antagonists. Analogues 15 and 16 were able to inhibit to some extent the stimulation of T cells by the immunodominant MBP83-99 peptide from immunized mice. Inhibition was followed to a lesser degree by analogues 17 and 18 and then by analogue 19. These studies show that lead compounds 15 and 16 may be used for immunotherapy against MS.
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35
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Uncini A, Shahrizaila N, Kuwabara S. Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes. J Neurol Neurosurg Psychiatry 2017; 88:266-271. [PMID: 27799296 DOI: 10.1136/jnnp-2016-314310] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 10/14/2016] [Indexed: 01/12/2023]
Abstract
In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.
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Affiliation(s)
- Antonino Uncini
- Department of Neuroscience, Imaging and Clinical Sciences, University 'G. d'Annunzio' Chieti-Pescara, Chieti, Italy
| | | | - Satoshi Kuwabara
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
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36
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Fan C, Jin H, Hao H, Gao F, Sun Y, Lu Y, Liu Y, Lv P, Cui W, Teng Y, Huang Y. Anti-ganglioside antibodies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients. Muscle Nerve 2016; 55:470-475. [PMID: 27464289 DOI: 10.1002/mus.25266] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 07/17/2016] [Accepted: 07/22/2016] [Indexed: 01/04/2023]
Abstract
INTRODUCTION In this study we investigated the relationships between anti-ganglioside antibodies and Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. RESULTS In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. CONCLUSIONS These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470-475, 2017.
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Affiliation(s)
- Chenghe Fan
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Haiqiang Jin
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Hongjun Hao
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Feng Gao
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Yongan Sun
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Yuanyuan Lu
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Yuanyuan Liu
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Pu Lv
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Wei Cui
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Yuming Teng
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
| | - Yining Huang
- Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China
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Jasti AK, Selmi C, Sarmiento-Monroy JC, Vega DA, Anaya JM, Gershwin ME. Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment. Expert Rev Clin Immunol 2016. [DOI: 10.1080/1744666x.2016.1193006 10.1080/1744666x.2016.1193006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Rosenbaum JT, Asquith MJ. The Microbiome: a Revolution in Treatment for Rheumatic Diseases? Curr Rheumatol Rep 2016; 18:62. [DOI: 10.1007/s11926-016-0614-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Gross S, Fischer A, Rosati M, Matiasek L, Corlazzoli D, Cappello R, Porcarelli L, Harcourt-Brown T, Jurina K, Garosi L, Flegel T, Quitt P, Molin J, Huelsmeyer VI, Schenk H, Gandini G, Gnirs K, Blot S, Jeandel A, Baroni M, Loderstedt S, Abbiati G, Leithaeuser C, Schulze S, Kornberg M, Lowrie M, Matiasek K. Nodo-paranodopathy, internodopathy and cleftopathy: Target-based reclassification of Guillain-Barré-like immune-mediated polyradiculoneuropathies in dogs and cats. Neuromuscul Disord 2016; 26:825-836. [PMID: 27743643 DOI: 10.1016/j.nmd.2016.08.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 07/14/2016] [Accepted: 08/29/2016] [Indexed: 01/23/2023]
Abstract
Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions. We identified that immune responses were directed either at Schmidt-Lanterman clefts, the paranode-node complex or both. Based on infiltrative and non-inflammatory changes, four subtypes and/or stages were distinguished, some of which indicate localisation of primary target antigens while others represent convergent late stage pictures, as a consequence to epitope spreading. The impact of histological subtyping onto clinical management and prognosis remains to be evaluated in future clinical trials. Natural development and clinical manifestation of large animal dysimmune neuropathy may reflect human Guillain-Barré syndrome more accurately than experimental models and therefore provide complementary clues for translational research.
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Affiliation(s)
- Simone Gross
- Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Andrea Fischer
- Section of Neurology, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, München, Munich, Germany
| | - Marco Rosati
- Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Lara Matiasek
- Neurology Referral Service, Tierklinik Haar, Haar, Germany
| | | | | | | | - Tom Harcourt-Brown
- Section of Neurology, Langford Veterinary Services, University of Bristol, Bristol, UK
| | - Konrad Jurina
- Section of Neurology, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, München, Munich, Germany
| | - Laurent Garosi
- Neurology Referral Service, Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, UK
| | - Thomas Flegel
- Neurology Unit, Department of Small Animal Medicine, University of Leipzig, Leipzig, Germany
| | - Pia Quitt
- Section of Neurology, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, München, Munich, Germany
| | - Jessica Molin
- Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Velia-Isabel Huelsmeyer
- Section of Neurology, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, München, Munich, Germany
| | - Henning Schenk
- Neurology Service, Tierklinik Lueneburg, Lueneburg, Germany
| | - Gualtiero Gandini
- Department of Veterinary Medical Science, University of Bologna, Italy
| | - Kirsten Gnirs
- Section of Neurology & Neurosurgery, Advetia Clinic for Small Animal Medicine, Paris, France
| | - Stéphane Blot
- Section of Neurologie, Ecole Nationale Vétérinaire d'Alfort, University of Paris Est, Maisons Alfort, France
| | - Aurélien Jeandel
- Section of Neurologie, Ecole Nationale Vétérinaire d'Alfort, University of Paris Est, Maisons Alfort, France
| | - Massimo Baroni
- Section of Neurology, Clinica Veterinaria Valdinievole, Monsummano, Italy
| | - Shenja Loderstedt
- Section of Neurology, Clinic of Small Animal Medicine, University of Berlin, Berlin, Germany
| | | | | | | | | | - Mark Lowrie
- Dovecote Veterinary Hospital, Castle Donington, UK
| | - Kaspar Matiasek
- Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
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Jasti AK, Selmi C, Sarmiento-Monroy JC, Vega DA, Anaya JM, Gershwin ME. Guillain-Barré syndrome: causes, immunopathogenic mechanisms and treatment. Expert Rev Clin Immunol 2016; 12:1175-1189. [PMID: 27292311 DOI: 10.1080/1744666x.2016.1193006] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Guillain-Barré syndrome is a rare disease representing the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month. The etiology and pathogenesis remain largely enigmatic and the syndrome results in death or severe disability in 9-17% of cases despite immunotherapy. Areas covered: In terms of etiology, Guillain-Barré syndrome is linked to Campylobacter infection but less than 0.1% of infections result in the syndrome. In terms of pathogenesis, activated macrophages and T cells and serum antibodies against gangliosides are observed but their significance is unclear. Expert commentary: Guillain-Barré syndrome is a heterogeneous condition with numerous subtypes and recent data point towards the role of ganglioside epitopes by immunohistochemical methods. Ultimately, the syndrome results from a permissive genetic background on which environmental factors, including infections, vaccination and the influence of aging, lead to disease.
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Affiliation(s)
- Anil K Jasti
- a Division of Rheumatology, Allergy, and Clinical Immunology , University of California Davis , Davis , CA , USA
| | - Carlo Selmi
- b Rheumatology and Clinical Immunology , Humanitas Research Hospital , Rozzano , Milan , Italy.,c BIOMETRA Department , University of Milan , Milan , Italy
| | - Juan C Sarmiento-Monroy
- d Center for Autoimmune Diseases Research (CREA) , Universidad del Rosario , Bogota , Colombia
| | - Daniel A Vega
- e Intensive Care Unit, Mederi, Hospital Universitario Mayor , Universidad del Rosario , Bogotá , Colombia
| | - Juan-Manuel Anaya
- d Center for Autoimmune Diseases Research (CREA) , Universidad del Rosario , Bogota , Colombia
| | - M Eric Gershwin
- a Division of Rheumatology, Allergy, and Clinical Immunology , University of California Davis , Davis , CA , USA
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Croxford JL, Miyake S. Animal Models for the Study of Neuroimmunological Disease. NEUROIMMUNOLOGICAL DISEASES 2016. [PMCID: PMC7122656 DOI: 10.1007/978-4-431-55594-0_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/29/2022]
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Gutlapalli VR, Sykam A, Nayarisseri A, Suneetha S, Suneetha LM. Insights from the predicted epitope similarity between Mycobacterium tuberculosis virulent factors and its human homologs. Bioinformation 2015; 11:517-24. [PMID: 26770024 PMCID: PMC4702028 DOI: 10.6026/97320630011517] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Revised: 12/13/2015] [Accepted: 12/13/2015] [Indexed: 01/22/2023] Open
Abstract
Mycobacterium tuberculosis is known to be associated with several autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis and multiple sclerosis. This is attributed to sequence similarity between virulent factors and human proteins. Therefore, it is of interest to identify such regions in the virulent factors to assess potential autoimmune related information. M. tb specific virulent factors were downloaded from the VFDB database and its human homologs were identified using the sequence comparison search tool BLASTP. Both virulent proteins and their corresponding human homologs were further scanned for epitopes (B cell and HLA class I and II allele specific) using prediction programs (BCPRED and NETMHC). Data shows the presence of matching 22 B-cell, 79 HLA class II and 16 HLA class I specific predicted epitopes in these virulent factors having human homologs. A known peptide (HAFYLQYKNVKVDFA) associated with autoimmune atopic dermatitis is shown in the superoxide dismutase homolog structures of the bacterium (PDB ID: 1IDS) and human (PDB ID: 2QKC). This data provides insight into the understanding of infection-associated auto-immunity.
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Affiliation(s)
- Venkata Ravi Gutlapalli
- CODEWEL Nireekshana-ACET, Hyderabad, Telangana-500029, India
- Centre for Biotechnology, AcharyaNagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh 522510, India
| | - Aparna Sykam
- CODEWEL Nireekshana-ACET, Hyderabad, Telangana-500029, India
- Centre for Biotechnology, AcharyaNagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh 522510, India
| | - Anuraj Nayarisseri
- Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore - 452010, Madhya Pradesh, India
| | - Sujai Suneetha
- CODEWEL Nireekshana-ACET, Hyderabad, Telangana-500029, India
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Vegosen L, Breysse PN, Agnew J, Gray GC, Nachamkin I, Sheikh K, Kamel F, Silbergeld E. Occupational Exposure to Swine, Poultry, and Cattle and Antibody Biomarkers of Campylobacter jejuni Exposure and Autoimmune Peripheral Neuropathy. PLoS One 2015; 10:e0143587. [PMID: 26636679 PMCID: PMC4670215 DOI: 10.1371/journal.pone.0143587] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 11/07/2015] [Indexed: 01/10/2023] Open
Abstract
INTRODUCTION Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed. METHODS Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals) and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher's Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies. RESULTS Farmers had significantly higher levels of anti-C. jejuni IgA (p < 0.0001) and IgG (p = 0.02) antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21%) tested positive for anti-ganglioside autoantibodies compared to non-farmers (9%), but this difference was not statistically significant (p = 0.11). There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies. CONCLUSIONS The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to reduce occupational exposure to C. jejuni should be considered.
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Affiliation(s)
- Leora Vegosen
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
- * E-mail:
| | - Patrick N. Breysse
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
| | - Jacqueline Agnew
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
| | - Gregory C. Gray
- Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, United States of America
| | - Irving Nachamkin
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Kazim Sheikh
- Department of Neurology, University of Texas Medical School, Houston, TX, United States of America
| | - Freya Kamel
- Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, United States of America
| | - Ellen Silbergeld
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
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Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V. Molecules 2015; 20:6913-24. [PMID: 25913930 PMCID: PMC6272744 DOI: 10.3390/molecules20046913] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/09/2015] [Accepted: 04/14/2015] [Indexed: 12/19/2022] Open
Abstract
α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer).
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Shahrizaila N, Kokubun N, Sawai S, Umapathi T, Chan YC, Kuwabara S, Hirata K, Yuki N. Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes. Neurology 2014; 83:118-24. [PMID: 24920848 DOI: 10.1212/wnl.0000000000000577] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barré syndrome subtypes and clinical features. METHODS In acute sera from 199 patients with Guillain-Barré syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside complexes were tested using ELISA against individual antigens from single glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from the combination of 2 different glycolipids. Based on serial nerve conduction studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85 axonal subtypes, and 45 unclassified. RESULTS Significant associations were detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1, GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or complex of LM1/GA1. No significant association was demonstrated between acute inflammatory demyelinating polyneuropathy and any of the glycolipids or ganglioside complexes. Anti-ganglioside complex antibodies alone were detected in 7 patients (5 axonal subtype). CONCLUSIONS The current study demonstrates that antibodies to single glycolipids and ganglioside complexes are associated with acute motor axonal neuropathy or acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that antibodies to glycolipids are increased in patients with acute motor axonal neuropathy and acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy.
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Affiliation(s)
- Nortina Shahrizaila
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Norito Kokubun
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Setsu Sawai
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Thirugnanam Umapathi
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Yee-Cheun Chan
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Satoshi Kuwabara
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Koichi Hirata
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore
| | - Nobuhiro Yuki
- From the Faculty of Medicine (N.S.), University of Malaya, Kuala Lumpur, Malaysia; Dokkyo Medical University (N.K., K.H.), Tochigi, Japan; Graduate School of Medicine (S.S., S.K.), Chiba University, Japan; National Neurosciences Institute (T.U.), Singapore; and National University Singapore (Y.-C.C., N.Y.), Singapore.
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The Clinical Significance of Posttranslational Modification of Autoantigens. Clin Rev Allergy Immunol 2014; 47:73-90. [DOI: 10.1007/s12016-014-8424-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Abstract
Guillain-Barré syndrome (GBS) is an acute, immune-mediated, postinfectious polyneuropathy with symmetrical ascending weakness, diminished deep tendon reflexes, and nonspecific sensory symptoms. CSF protein is raised with normal or only slightly elevated cell count. Based on electrophysiological and pathological findings, a demyelinating variant (acute inflammatory demyelinating polyneuropathy, AIDP) and an axonal variant (acute motor axonal neuropathy, AMAN) can be differentiated. Molecular mimicry with common epitopes between infective agents and peripheral nerves is discussed as an important pathophysiological principle. The symptoms progress for a mean of 10 days (up to 4 weeks) and after a plateau of 1-2 weeks remit spontaneously. At the height of the disease 60% of children are unable to walk and 10-15% need artificial ventilation. Treatment with plasmapheresis and intravenous immunoglobulins (IVIG) has been proven in placebo-controlled studies in adults with severe disease to speed up recovery significantly. In children, mostly open studies have shown similar treatment effects, although their spontaneous course is frequently less severe. Children with GBS should be treated with IVIG when they have lost the ability to walk, or when they are still deteriorating significantly and are expected to lose the ability to walk. The long-term prognosis is more favorable than that in adults. Whereas 25% of patients maintain mild neurological symptoms and signs, disability in the long term is very rare and usually due to complications such as myelitic involvement or chronic inflammatory demyelinating polyneuropathy (CIDP).
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Wakerley BR, Yuki N. Infectious and noninfectious triggers in Guillain-Barré syndrome. Expert Rev Clin Immunol 2014; 9:627-39. [PMID: 23899233 DOI: 10.1586/1744666x.2013.811119] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Guillain-Barré syndrome (GBS) is the commonest cause of acquired flaccid paralysis in the world and regarded by many as the prototype for postinfectious autoimmunity. Here the authors consider both infectious and noninfectious triggers of GBS and determine where possible what immunological mechanisms may account for this association. In approximately two-thirds of cases, an infectious trigger is reported in the weeks that lead up to disease onset, indicating that the host's response to infection must play an important role in disease pathogenesis. The most frequently identified bacteria, Campylobacter jejuni, through a process known as molecular mimicry, has been shown to induce cross-reactive anti-ganglioside antibodies, which can lead to the development of axonal-type GBS in some patients. Whether this paradigm can be extended to other infectious organisms or vaccines remains an important area of research and has public health implications. GBS has also been reported rarely in patients with underlying systemic diseases and immunocompromised states and although the exact mechanism is yet to be established, increased susceptibility to known infectious triggers should be considered most likely.
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Affiliation(s)
- Benjamin R Wakerley
- Department of Medicine, National University Hospital, 1E Kent Ridge Road, Singapore.
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How Do Gangliosides Regulate RTKs Signaling? Cells 2013; 2:751-67. [PMID: 24709879 PMCID: PMC3972652 DOI: 10.3390/cells2040751] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 11/19/2013] [Accepted: 11/27/2013] [Indexed: 01/14/2023] Open
Abstract
Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are located on the outer leaflet of the plasma membrane in glycolipid-enriched microdomains, where they interact with molecules of signal transduction pathways including receptors tyrosine kinases (RTKs). The role of gangliosides in the regulation of signal transduction has been reported in many cases and in a large number of cell types. In this review, we summarize the current knowledge on the biosynthesis of gangliosides and the mechanism by which they regulate RTKs signaling.
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Epps SVR, Harvey RB, Hume ME, Phillips TD, Anderson RC, Nisbet DJ. Foodborne Campylobacter: infections, metabolism, pathogenesis and reservoirs. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2013; 10:6292-304. [PMID: 24287853 PMCID: PMC3881114 DOI: 10.3390/ijerph10126292] [Citation(s) in RCA: 163] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/08/2013] [Accepted: 11/09/2013] [Indexed: 11/17/2022]
Abstract
Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions.
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Affiliation(s)
- Sharon V. R. Epps
- Food & Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA; E-Mails: (R.B.H.); (M.E.H.); (D.J.N)
- Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77845, USA; E-Mails: (S.V.R.E.); (T.D.P.)
| | - Roger B. Harvey
- Food & Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA; E-Mails: (R.B.H.); (M.E.H.); (D.J.N)
| | - Michael E. Hume
- Food & Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA; E-Mails: (R.B.H.); (M.E.H.); (D.J.N)
| | - Timothy D. Phillips
- Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77845, USA; E-Mails: (S.V.R.E.); (T.D.P.)
| | - Robin C. Anderson
- Food & Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA; E-Mails: (R.B.H.); (M.E.H.); (D.J.N)
| | - David J. Nisbet
- Food & Feed Safety Research Unit, Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX 77845, USA; E-Mails: (R.B.H.); (M.E.H.); (D.J.N)
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