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Xu X, Ying H, Wang X, Hong W, Zhang M. Identification of Angiogenesis-Related Gene Signatures and Prediction of Potential Therapeutic Targets in Ulcerative Colitis Using Integrated Bioinformatics. J Inflamm Res 2024; 17:11699-11717. [PMID: 39741751 PMCID: PMC11687120 DOI: 10.2147/jir.s478880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 12/10/2024] [Indexed: 01/03/2025] Open
Abstract
Objective This study aims to clarify angiogenesis mechanisms in ulcerative colitis and identify potential therapeutic targets. Methods The Gene Expression Omnibus (GEO) database was used to obtain expression profiles and clinical data for UC and healthy colon tissues. Angiogenesis-related gene sets were acquired from GeneCards. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified UC-associated hub genes. The CIBERSORT algorithm assessed immune cell infiltration. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to determine biological mechanisms. External datasets were utilized to validate and characterize the angiogenesis-related genes in relation to biological agents. Additionally, an ulcerative colitis mouse model was constructed to verify the key genes' expression using real-time quantitative PCR. To predict potential therapeutic agents, we used the DGIdb database. Molecular docking modeled small molecule binding conformations to key gene targets. Results This study identified 1,247 DEGs enriched in inflammatory/immune pathways from UC and healthy colon samples. WGCNA indicated the black and light cyan modules were most relevant. Intersecting these with 89 angiogenesis genes revealed 5 UC-associated hub genes (pdgfrb, vegfc, angpt2, tnc, hgf). Validation via ROC analysis, differential expression, and a mouse model confirmed upregulation, supporting their potential as UC diagnostic biomarkers. Bioinformatics approaches like protein-protein interaction, enrichment analysis, and GSEA revealed involvement in PDGFR and PI3K-Akt signaling pathways. CIBERSORT analysis of immune cell infiltration showed positive correlations between the key genes and various immune cells, especially neutrophils, highlighting angiogenesis-inflammation interplay in UC. A ceRNA network was constructed. Drug prediction and molecular docking revealed potential UC therapies like sunitinib and imatinib targeting angiogenesis. Conclusion This study identified and validated five angiogenesis-related genes (pdgfrb, vegfc, angpt2, tnc, hgf) that may serve as diagnostic biomarkers and drug targets for UC.
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Affiliation(s)
- Xijuan Xu
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China
| | - Hongan Ying
- Department of Geriatrics, Taizhou First People’s Hospital, Taizhou, People’s Republic of China
| | - Xiaozhi Wang
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China
| | - Weiwen Hong
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China
| | - Meng Zhang
- Department of General Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China
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Gugliesi F, Pasquero S, Griffante G, Scutera S, Albano C, Pacheco SFC, Riva G, Dell’Oste V, Biolatti M. Human Cytomegalovirus and Autoimmune Diseases: Where Are We? Viruses 2021; 13:260. [PMID: 33567734 PMCID: PMC7914970 DOI: 10.3390/v13020260] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 12/14/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the β-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.
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Affiliation(s)
- Francesca Gugliesi
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Selina Pasquero
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Gloria Griffante
- Department of Translational Medicine, Molecular Virology Unit, University of Piemonte Orientale Medical School, 28100 Novara, Italy;
| | - Sara Scutera
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Camilla Albano
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Sergio Fernando Castillo Pacheco
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Giuseppe Riva
- Otorhinolaryngology Division, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy;
| | - Valentina Dell’Oste
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Matteo Biolatti
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
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Fisher MA, Lloyd ML. A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease-Do Mice Lie? Int J Mol Sci 2020; 22:ijms22010214. [PMID: 33379272 PMCID: PMC7795257 DOI: 10.3390/ijms22010214] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/10/2020] [Accepted: 12/17/2020] [Indexed: 12/12/2022] Open
Abstract
Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model.
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Affiliation(s)
- Michelle A. Fisher
- Division of Infection and Immunity, School of Biomedical Sciences, The University of Western Australia, Nedlands 6009, Australia;
| | - Megan L. Lloyd
- Division of Infection and Immunity, School of Biomedical Sciences, The University of Western Australia, Nedlands 6009, Australia;
- Marshall Centre for Infectious Diseases Research and Training, Division of Infection and Immunity, School of Biomedical Sciences, The University of Western Australia, Nedlands 6009, Australia
- Correspondence:
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Yokoyama Y, Yamakawa T, Hirano T, Kazama T, Hirayama D, Wagatsuma K, Nakase H. Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data. Int J Mol Sci 2020; 21:ijms21072438. [PMID: 32244555 PMCID: PMC7177554 DOI: 10.3390/ijms21072438] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/28/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.
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Arslan F, Vahaboglu H. Phantom of the inflammasome in the gut: Cytomegalovirus. World J Meta-Anal 2019; 7:346-349. [DOI: 10.13105/wjma.v7.i7.346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 07/25/2019] [Accepted: 07/29/2019] [Indexed: 02/06/2023] Open
Abstract
Cytomegalovirus (CMV) is frequently detected in inflammatory bowel tissue, especially in corticosteroid-refractory patients, and it has been blamed for adverse outcomes. However, the first acquisition of CMV does not involve the colon. In particular in the colonic mucosa, which evolved due to the gut microbial relationship, CMV promotes inflammation via recruited monocytes and not through replication in resident macrophages. Whether CMV is the last straw in the process of mucosal inflammation, a doomed agent, or an innocent bystander is a difficult question that remains elusive. With this work, we will try to review the relationship between intestinal mucosa and CMV in the framework of basic virological principles.
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Affiliation(s)
- Ferhat Arslan
- Department of Infectious Diseases and Clinical Microbiology, Istanbul Medeniyet University, Istanbul 34722, Turkey
| | - Haluk Vahaboglu
- Department of Infectious Diseases and Clinical Microbiology, Istanbul Medeniyet University, Istanbul 34722, Turkey
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Nakase H, Herfarth H. Cytomegalovirus Colitis, Cytomegalovirus Hepatitis and Systemic Cytomegalovirus Infection: Common Features and Differences. Inflamm Intest Dis 2016; 1:15-23. [PMID: 27243020 PMCID: PMC4883584 DOI: 10.1159/000443198] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cytomegalovirus (CMV) is a ubiquitous human herpes virus, which, after often asymptomatic primary infection, establishes a lifelong latent infection that can periodically be reactivated in both immunocompetent and immunosuppressed carriers. Whereas the diagnostic approach in case of a suspicion of CMV reactivation is well defined, the indication for antiviral therapy can often only be made in the context of an extent of organ involvement, the immune status, and comorbidities of the patient. This article reviews the epidemiology, diagnosis, and therapy of CMV reactivation with a focus on inflammatory bowel diseases and potentially different diagnostic and therapeutic approaches in Asia and the Western world.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Division of Endoscopy, Kyoto University Hospital, Kyoto, Japan
| | - Hans Herfarth
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, N.C., USA
- *Hans Herfarth, MD, PhD, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Bioinformatics Bldg., CB No. 7080, Chapel Hill, NC 27599 (USA), E-Mail
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Liu CC, Zhang ZY. Relationship between cytomegalovirus infection and inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2015; 23:1784-1790. [DOI: 10.11569/wcjd.v23.i11.1784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (HCMV) is a common opportunistic pathogenic virus, which causes dormant or latent infection following primary infection in immunocompetent individuals and overt infection in immunocompromised patients. Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory illness and patients with IBD are often immunosuppressed, through combined action of potentially malnutrition, use of immunosuppressants, etc. These factors predispose patients with IBD to an increased risk of developing HCMV infection. The number of IBD patients with concomitant HCMV infection is increasing and the adverse role of HCMV in IBD has drawn much attention from clinicians. Recent evidence suggests that HCMV may play an essential role in the progression of IBD, and elucidating the possible association between HCMV infection and IBD as well as the underlying mechanisms has great diagnostic and therapeutic implications. Here we review the possible relationship between HCMV and IBD.
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Brunson JL, Becker F, Stokes KY. The impact of primary and persistent cytomegalovirus infection on the progression of acute colitis in a murine model. ACTA ACUST UNITED AC 2014; 22:31-7. [PMID: 25511533 DOI: 10.1016/j.pathophys.2014.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 11/06/2014] [Accepted: 11/07/2014] [Indexed: 12/25/2022]
Abstract
Cytomegalovirus (CMV) infects 60-100% of the population worldwide. CMV has been implicated in many diseases through the induction of inflammation. Inflammatory bowel disease (IBD) affects over 1 million Americans annually. IBD, in particular ulcerative colitis, has been associated with CMV infection. Here we use a murine model to test if both primary and persistent CMV infections exacerbate colitis. C57Bl/6J mice were injected with Mock inoculum or murine CMV (mCMV) 4d (primary infection) or 6wks (persistent infection) before inducing colitis. Colitis was induced by administering 3% DSS (dextran sodium sulfate) in the drinking water for 6 days. Distilled water was given to controls. Disease activity index (DAI), derived from scores for stool consistency, body weight loss, occult blood, and rectal bleeding, was recorded daily. DAI increased early with DSS treatment in Mocks when compared with water-treated controls. This was accelerated by both primary and persistent mCMV and appeared to be primarily due to the earlier appearance of gross bleeding vs. their Mock controls. Mocks reached similar DAI values by day 6. Myeloperoxidase was modestly elevated in the mCMV 4d-DSS over the Mock 4d-DSS, however there was no such synergism in the 6wk groups. Histology was comparable in Mock and mCMV groups. Taken together our findings show that mCMV accelerated the development of acute colitis although a milder model of colitis may be needed to better delineate the impact of the virus on disease progression. Further work focusing on disruption of barrier function and bleeding may help determine the underlying mechanisms.
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Affiliation(s)
- Jerry L Brunson
- Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Molecular and Tumor Virology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Cardiovascular Disease and Sciences, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States
| | - Felix Becker
- Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Department of General and Visceral Surgery, University Hospital Muenster, Germany
| | - Karen Y Stokes
- Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Molecular and Tumor Virology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Cardiovascular Disease and Sciences, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States.
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Smith PD, Shimamura M, Musgrove LC, Dennis EA, Bimczok D, Novak L, Ballestas M, Fenton A, Dandekar S, Britt WJ, Smythies LE. Cytomegalovirus enhances macrophage TLR expression and MyD88-mediated signal transduction to potentiate inducible inflammatory responses. THE JOURNAL OF IMMUNOLOGY 2014; 193:5604-12. [PMID: 25355920 DOI: 10.4049/jimmunol.1302608] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Circulating monocytes carrying human CMV (HCMV) migrate into tissues, where they differentiate into HCMV-infected resident macrophages that upon interaction with bacterial products may potentiate tissue inflammation. In this study, we investigated the mechanism by which HCMV promotes macrophage-orchestrated inflammation using a clinical isolate of HCMV (TR) and macrophages derived from primary human monocytes. HCMV infection of the macrophages, which was associated with viral DNA replication, significantly enhanced TNF-α, IL-6, and IL-8 gene expression and protein production in response to TLR4 ligand (LPS) stimulation compared with mock-infected LPS-stimulated macrophages during a 6-d in vitro infection. HCMV infection also potentiated TLR5 ligand-stimulated cytokine production. To elucidate the mechanism by which HCMV infection potentiated inducible macrophage responses, we show that infection by HCMV promoted the maintenance of surface CD14 and TLR4 and TLR5, which declined over time in mock-infected macrophages, and enhanced both the intracellular expression of adaptor protein MyD88 and the inducible phosphorylation of IκBα and NF-κB. These findings provide additional information toward elucidating the mechanism by which HCMV potentiates bacteria-induced NF-κB-mediated macrophage inflammatory responses, thereby enhancing organ inflammation in HCMV-infected tissues.
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Affiliation(s)
- Phillip D Smith
- Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; Veterans Affairs Medical Center, Birmingham, AL 35233;
| | - Masako Shimamura
- Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Lois C Musgrove
- Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Evida A Dennis
- Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Diane Bimczok
- Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Lea Novak
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; and
| | - Mary Ballestas
- Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Anne Fenton
- Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA 95616
| | - Satya Dandekar
- Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA 95616
| | - William J Britt
- Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294
| | - Lesley E Smythies
- Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; and
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Yamada S, Yoshino T, Matsuura M, Minami N, Toyonaga T, Honzawa Y, Tsuji Y, Nakase H. Long-term efficacy of infliximab for refractory ulcerative colitis: results from a single center experience. BMC Gastroenterol 2014; 14:80. [PMID: 24758588 PMCID: PMC4012244 DOI: 10.1186/1471-230x-14-80] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Accepted: 04/16/2014] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The long-term efficacy of infliximab (IFX) for patients with refractory ulcerative colitis (UC) is unclear. The aim of this study was to assess the long-term outcomes of IFX treatment in patients with refractory UC. METHODS Thirty-three patients with refractory UC who received IFX treatment at Kyoto University Hospital between 2003 and 2013 were retrospectively evaluated. IFX intensification was defined as a dose escalation (up to 10 mg/kg) and/or shorter intervals between infusions (every 4-6 weeks). RESULTS Of the 33 patients who received scheduled infusions of IFX, 24 (72.7%) achieved clinical remission within 8 weeks after initiating IFX treatment. Of these 24 responders, 17 (70.8%) experienced a relapse of UC and required IFX intensification, and 16 (66.7%) eventually maintained clinical remission with IFX treatment, including IFX intensification. Of the 33 patients, 6 (18.2%) underwent colectomy during IFX treatment. Multivariate regression analysis showed that a serum C-reactive protein (CRP) concentration <5 mg/L two weeks after starting IFX was a predictor of a positive clinical response to IFX induction therapy. No severe adverse events occurred in UC patients treated with IFX. CONCLUSION IFX intensification was necessary for long-term maintenance of remission and to prevent colectomy in patients with refractory UC.
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Affiliation(s)
| | | | | | | | | | | | | | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
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Nakase H, Honzawa Y, Toyonaga T, Yamada S, Minami N, Yoshino T, Matsuura M. Diagnosis and treatment of ulcerative colitis with cytomegalovirus infection: importance of controlling mucosal inflammation to prevent cytomegalovirus reactivation. Intest Res 2014; 12:5-11. [PMID: 25349558 PMCID: PMC4204682 DOI: 10.5217/ir.2014.12.1.5] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 12/27/2013] [Accepted: 12/27/2013] [Indexed: 12/16/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a member of the herpesvirus family. HCMV infection persists throughout the host lifespan in a latent state following primary infection. The ability of HCMV to escape control by the host immune system and its resulting reactivation suggests the importance of ongoing immune surveillance in the prevention of HCMV reactivation. HCMV is a common cause of opportunistic infection that causes severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), HCMV is often reactivated because these patients are frequently treated with immunosuppressive agents. This reactivation exacerbates colitis. Additionally, HCMV infection can induce severe colitis, even in patients with UC who have never been treated with immunosuppressive agents. However, the role of HCMV in colonic inflammation in patients with UC remains unclear. Here, we present previous and current clinical data on the diagnosis and treatment of HCMV infection in UC. Additionally, our experimental data from a newly established mouse model mimicking UC with concomitant CMV infection clearly demonstrate that inflammation could result in the exacerbation of UC disease activity with induction of HCMV reactivation. In summary, optimal control of colonic inflammation should be achieved in UC patients who are refractory to conventional immunosuppressive therapies and are positive for HCMV.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yusuke Honzawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiko Toyonaga
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoki Minami
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takuya Yoshino
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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