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Calise SJ, Chan EKL. Anti-rods/rings autoantibody and IMPDH filaments: an update after fifteen years of discovery. Autoimmun Rev 2020; 19:102643. [PMID: 32805424 DOI: 10.1016/j.autrev.2020.102643] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
Autoantibodies to unknown subcellular rod and ring-shaped structures were first discovered in sera from hepatitis C patients in 2005. Early studies showed a strong association between these anti-rods/rings antibodies (anti-RR) and the standard of care interferon-α plus ribavirin combination therapy (IFN/RBV), suggesting that anti-RR are drug-induced autoantibodies. In the context of hepatitis C, anti-RR have been linked with relapse from or lack of response to IFN/RBV in some patient cohorts. However, examples of anti-RR in other diseases and healthy individuals have also been reported over the years, although anti-RR remains a rare autoantibody response in general. The advent of new direct-acting antiviral drugs for chronic hepatitis C and studies of anti-RR from different parts of the world are also beginning to change the perception of anti-RR. The nucleotide biosynthetic enzyme inosine monophosphate dehydrogenase (IMPDH) has been identified as the major autoantigen recognized by anti-RR. Coincidentally, the assembly of IMPDH into micron-scale rod and ring-shaped structures was discovered around the same time as anti-RR. Knowledge of the fundamental biological properties and cellular functions of these structures, referred to as "IMPDH filaments" by cell biologists, has advanced in parallel to anti-RR antibodies. Recent studies have revealed that IMPDH filament assembly is a mechanism to prevent feedback inhibition of IMPDH and is therefore important for the increased nucleotide production required in hyperproliferating cells, like activated T cells. Fifteen years later, we review the history and current knowledge in both the anti-RR autoantibody and IMPDH filament fields. TAKE-HOME MESSAGE: Anti-rods/rings are recognized as an example of a drug-induced autoantibody in hepatitis C patients treated with interferon and ribavirin, although new studies suggest anti-rods/rings may be detected in other contexts and may depend on unknown environmental or genetic factors in different populations. Recent data suggest that the assembly of IMPDH into rod and ring structures, the targets of anti-rods/rings autoantibody, is a mechanism for hyperproliferating cells, like activated T cells, to maintain increased guanine nucleotide levels to support rapid cell division.
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Affiliation(s)
- S John Calise
- Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL 32610-0424, USA.
| | - Edward K L Chan
- Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL 32610-0424, USA.
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Nadir CD4 Is Negatively Associated With Antinuclear Antibody Detection in HCV/HIV-Coinfected Patients. J Acquir Immune Defic Syndr 2019; 80:461-466. [PMID: 30570526 DOI: 10.1097/qai.0000000000001940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) and HIV infections are associated with higher risk of autoimmune diseases and T-cell dysfunction. SETTING We evaluate prevalence and factors associated with the presence of autoimmune antinuclear (ANA), anti-smooth muscle actin (aSMA), and anti-liver kidney microsome (aLKM1) antibodies (Ab) in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era. METHODS A cross-sectional observational study nested in the ANRS CO13 HEPAVIH cohort (NCT number: NCT03324633). We selected patients with both ANA testing and T-cell immunophenotyping determination during the cohort follow-up and collected aLKM1 and aSMA data when available. Logistic regression models were built to determine factors associated with the presence of auto-Ab. RESULTS Two hundred twenty-three HCV/HIV-coinfected patients fulfilled selection criteria. Prevalence of ANA and aSMA was 43.5% and 23.2%, respectively, and both were detected in 13.3% of patients. Isolated aSMA were detected in 9.9% and aLKM1 in 2 patients. In multivariable analysis, only a low nadir CD4 T-cell count was significantly associated with ANA detection. CONCLUSIONS ANA and aSMA detection remain frequent in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era, despite fair immune restoration. These results advocate for a close monitoring of ANA before immune checkpoint inhibitor therapy in these patients with greater caution for those with a low nadir CD4 T-cell count.
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Emara M, Mohsen E, Shawky RM, El-Domany RA. Assessment of the Prevalence of Non-Organ-Specific Autoantibodies in Egyptian Patients with HCV. Immunol Invest 2019; 49:676-686. [PMID: 31820668 DOI: 10.1080/08820139.2019.1699108] [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: 10/25/2022]
Abstract
The relation between non-organ specific autoantibodies (NOSA) and hepatitis C virus (HCV) infection has been investigated within different communities resulting in different prevalence rates and patterns. The purpose of this study was to investigate the prevalence of some NOSA such as RF-IgG, ANA, ASMA, and LKM-1 in Egyptian patients with HCV group as compared with Egyptian healthy controls group. A total of 186 HCV positive serum samples in addition to 81 samples from healthy control were screened for the presence of some common autoantibodies (RF-IgG, ANA, ASMA, and LKM-1) using ELISA technique for ANA, ASMA, and LK-1 while RF-IgG was assayed by latex agglutination technique. The presence of these autoantibodies was tested in relation to some demographic variables and viral titers. Associations were assessed using logistic regression analysis adjusted for potential confounders. Among patients, 100 (53.7%) of 186 and 6 (7.4%) of 81 healthy control group were positive for at least one autoantibody. Furthermore, 2 patients (1%) were positive for three autoantibodies, whereas 22 patients (11.7%) were positive for 2 autoantibodies. The most prevalent autoantibody in anti-HCV-positive group was RF-IgG (87, 46.7%) followed by ASMA (26, 14%). The frequency of autoantibodies was bit higher in women as compared to men. Taken together, this study reports a non-significant difference in prevalence of NOSA between patients with HCV infection and healthy individuals except for ASMA. Likewise, no significant difference was found in prevalence of such autoantibodies when correlated with some demographic variables.
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Affiliation(s)
- Mohamed Emara
- Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University , Cairo, Egypt
| | - Esraa Mohsen
- Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University , Cairo, Egypt
| | - Riham M Shawky
- Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University , Cairo, Egypt
| | - Ramadan A El-Domany
- Department of Microbiology and Immunology, Faculty of Pharmacy, Kafr El sheikh University , Kafr el-Sheikh, Egypt
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Navarta LM, Espul CA, Acosta-Rivero N. High prevalence of a variety of autoantibodies in a population of hepatitis C virus-infected individuals. APMIS 2018; 126:515-522. [PMID: 29924449 DOI: 10.1111/apm.12850] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/24/2018] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection has been related to self-reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV-infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.
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Affiliation(s)
| | | | - Nelson Acosta-Rivero
- Centre for Protein Studies, Department of Biochemistry, Faculty of Biology, University of Havana, Havana, Cuba
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Kirdar S, Sener AG, Cengİz M, Aydin N. The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection. APMIS 2016; 124:979-984. [PMID: 27670736 DOI: 10.1111/apm.12593] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 07/11/2016] [Indexed: 12/12/2022]
Abstract
The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti-HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti-mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti-HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies.
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Affiliation(s)
- Sevİn Kirdar
- Department of Medical Microbiology, Adnan Menderes University, Aydin.
| | - Asli Gamze Sener
- Department of Medical Microbiology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, İzmir
| | - Merve Cengİz
- Department of Biostatistics, Adnan Menderes University, Aydin, Turkey
| | - Nerİman Aydin
- Department of Medical Microbiology, Adnan Menderes University, Aydin
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Narciso-Schiavon JL, Schiavon LDL. Autoantibodies in chronic hepatitis C: A clinical perspective. World J Hepatol 2015; 7:1074-1085. [PMID: 26052396 PMCID: PMC4450184 DOI: 10.4254/wjh.v7.i8.1074] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 01/16/2015] [Accepted: 02/04/2015] [Indexed: 02/06/2023] Open
Abstract
Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus (HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of gluten-related seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon (IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmune disease may be present or may be precipitated by IFN-based HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.
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Affiliation(s)
- Janaína Luz Narciso-Schiavon
- Janaína Luz Narciso-Schiavon, Leonardo de Lucca Schiavon, Department of Internal Medicine, Gastroenterology Division, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil
| | - Leonardo de Lucca Schiavon
- Janaína Luz Narciso-Schiavon, Leonardo de Lucca Schiavon, Department of Internal Medicine, Gastroenterology Division, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil
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Autoimmune hepatitis in patients with chronic HBV and HCV infections: patterns of clinical characteristics, disease progression and outcome. Ann Hepatol 2014. [PMID: 24378276 DOI: 10.1016/s1665-2681(19)30914-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
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Hamed ME, Kamal NM, Fouad MA, Raafat N. Study of non-organ-specific antibodies in Egyptian children with genotype-4 chronic hepatitis C. EGYPTIAN LIVER JOURNAL 2014; 4:1-7. [DOI: 10.1097/01.elx.0000440960.79233.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Hamed ME, Alanani NMK, Sherief LM, Fouad MA, Elwahab LA, Raafat N. Study of non-organ-specific antibodies in children with genotype 4 chronic hepatitis C. Saudi J Gastroenterol 2013; 19:262-270. [PMID: 24195980 PMCID: PMC3958974 DOI: 10.4103/1319-3767.121038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Accepted: 08/16/2013] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND/AIM Adult studies established a relationship between hepatitis C virus (HCV) infection and the presence of non-organ-specific antibodies (NOSAs). Most studies were carried out on genotypes 1 and 2. Only a few studies addressed that issue in pediatrics. No studies have been carried out on autoimmunity and genotype 4 in children. We aim to investigate NOSAs in 80 Egyptian children with chronic HCV infection along with studying the underlying genotype of HCV, and correlating autoimmunity with the epidemiological, clinical, biochemical, and virological features. MATERIALS AND METHODS HCV-RNA was assayed by the polymerase chain reaction and viral genotypes were determined. NOSAs were measured and liver biopsies were taken for histopathological examination. RESULTS Genotype 4 was the only detected genotype in the included 80 patients. Anti-smooth muscle antibodies (ASMA) were the only detected antibodies in 32 (40%) patients, always with V specificity (vessels only) at titers ranging from 1:20 and 1:160. Anti-nuclear antibodies (ANA) and liver-kidney microsomal antibodies-1 (LKMA-1) were not detected in any of our patients. Epidemiologic and clinical features did not significantly differ between autoantibody-positive and -negative patients. Among biochemical features, significantly high levels of total bilirubin, albumin, immunoglobulins, alkaline phosphatase, and gamma-glutamyl transpeptidase were found in the antibody-positive group. CONCLUSION Genotype 4 HCV is the prevailing genotype in Egyptian children with chronic HCV infection. A consistent proportion of these children with chronic HCV infection circulate non-organ-specific autoantibodies. The prevalence of ASMA and the absence of ANA and LKMA-1 might be related to the unique situation in Egypt with unique prevalence of genotype 4. More studies are warranted on larger pediatric population to validate these findings.
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Affiliation(s)
- Mohammed E. Hamed
- Department of Pediatric Hepatology, Faculty of Medicine, Zagazig University, Egypt
| | | | - Laila M. Sherief
- Department of Pediatrics, Faculty of Medicine, Zagazig University, Egypt
| | - Mohammed A. Fouad
- Department of Pathology, Faculty of Medicine, Zagazig University, Egypt
| | | | - Nermin Raafat
- Clinical Pathology, Faculty of Medicine, Zagazig University, Egypt
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Mauss S, Berger F, Schober A, Moog G, Heyne R, John C, Pape S, Hueppe D, Pfeiffer-Vornkahl H, Alshuth U. Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome. J Viral Hepat 2013; 20:e72-7. [PMID: 23490392 DOI: 10.1111/jvh.12011] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Accepted: 08/01/2012] [Indexed: 12/13/2022]
Abstract
Autoantibodies in hepatitis C virus-infected patients may indicate autoimmune hepatitis or other immune-mediated diseases. This may impact safety and efficacy of interferon-based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched-pair analysis was performed matching one autoantibody-positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.
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Affiliation(s)
- S Mauss
- Center for HIV and Hepatogastroenterology, Dusseldorf, Germany.
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Johanet C, Ballot E. Autoantibodies in autoimmune hepatitis: anti-liver kidney microsome type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) antibodies. Clin Res Hepatol Gastroenterol 2013; 37:216-8. [PMID: 23523312 DOI: 10.1016/j.clinre.2013.02.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Accepted: 02/07/2013] [Indexed: 02/06/2023]
Affiliation(s)
- Catherine Johanet
- Unité d'immunologie, CHU Saint-Antoine, AP-HP, 75571 Paris cedex 12, France.
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12
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Stinton LM, Myers RP, Coffin CS, Fritzler MJ. Clinical associations and potential novel antigenic targets of autoantibodies directed against rods and rings in chronic hepatitis C infection. BMC Gastroenterol 2013; 13:50. [PMID: 23506439 PMCID: PMC3606316 DOI: 10.1186/1471-230x-13-50] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Accepted: 03/12/2013] [Indexed: 01/11/2023] Open
Abstract
Background Chronic hepatitis C virus (HCV) infection is frequently associated with extrahepatic autoimmune disorders while interferon (IFN) and ribavirin treatment may exacerbate these conditions. Autoantibodies from HCV patients identify a novel indirect immunofluorescence (IIF) pattern on HEp-2 cells characterized by cytoplasmic rods and rings (RR). Our objectives were to determine the prevalence and clinical associations of RR autoantibodies in HCV patients, and identify related novel autoantibody targets. Methods Sera from 315 patients with HCV (301 treatment naive, 14 treated with interferon and/or ribavirin) were analyzed for the presence of RR antibodies by IIF on commercially available HEp-2 cell substrates. Antibodies to inosine monophosphate dehydrogenase 2 (IMPDH2) and cytidine triphosphate synthase 1 (CTPS1) were detected by addressable laser bead assay and other potential targets were identified by immunoscreening a protein microarray. Clinical and demographic data including HCV genotype, mode of infection, prior antiviral therapy, and histological findings were compared between RR antibody positive (RR+) and negative (RR-) patients. Results The median age of the HCV cohort was 51 years, 61% were male, and 76% were infected with HCV genotype 1 (G1). Four percent (n=14) had been treated with IFN-based therapy (IFN monotherapy, n=3; IFN/ribavirin, n=11); all had a sustained virologic response. In total, 15 patients (5% of the cohort) were RR+. RR+ and RR- patients had similar demographic and clinical characteristics including age, sex, mode of HCV infection, prevalence of the G1 HCV genotype, and moderate to severe fibrosis. Nevertheless, RR+ patients were significantly more likely than RR- cases to have been treated with IFN-based therapy (33% vs. 3%; adjusted odds ratio 20.5 [95% confidence interval 5.1-83.2]; P<0.0005). Only 1/10 RR positive sera had detectable antibodies to IMPHD2 and none had antibodies to CTPS1. Potentially important autoantibody targets identified on protein arrays included Myc-associated zinc finger protein (MAZI) and ankyrin repeat motif. Conclusion The majority of HCV patients with RR autoantibodies previously received IFN/ribavirin antiviral therapy. Further studies are necessary to determine the genesis of intracellular RR and elucidate the clinically relevant autoantigens as well as the clinical and prognostic significance of their cognate autoantibodies.
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Affiliation(s)
- Laura M Stinton
- Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
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Abstract
Combination therapy with pegylated interferon and ribavirin is the standard of care (SOC) for the treatment of chronic hepatitis C (CHC). Treating CHC with SOC may show a sustained virological response (SVR) in approximately 50-70 % of genotype 1 CHC patients and an SVR in 70-90 % of genotype 2 CHC patients. The genotype, baseline viral load, and viral kinetics (i.e., rapid virologic response and early virologic response) can be used as predictors of response-guided therapy. Nonetheless, host factors, e.g. age, ethnicity, insulin resistance, and genetic variations, may also play important roles in the SVR in CHC patients treated with SOC. Recent genome-wide association studies have demonstrated that single-nucleotide polymorphisms near the interleukin 28B gene (IL28B) were associated with SVR to treatment with SOC in CHC patients. The IL28B polymorphisms may contribute to the viral kinetics during treatment. Asian people have favorable IL28B polymorphisms. This factor may at least partly explain the high eradication rate of hepatitis C by SOC in Asia. Combination therapy with direct-acting antivirals (DAAs) and SOC can increase the SVR rates both in treatment-naïve and treatment-experienced patients. Although the IL28B polymorphisms also affect the SVR of triple therapy with SOC and first-generation protease inhibitors, pilot studies have demonstrated that potent DAAs might overcome the influence of IL28B polymorphisms. Thus, the treatment of hepatitis C virus infection could be simplified in the near future.
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Affiliation(s)
- Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Shih-Chuan 1st Road, Kaohsiung, Taiwan.
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Daschakraborty S, Aggarwal A, Aggarwal R. Non-organ-specific autoantibodies in Indian patients with chronic liver disease. Indian J Gastroenterol 2012; 31:237-42. [PMID: 22941677 DOI: 10.1007/s12664-012-0247-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2011] [Accepted: 08/15/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Autoantibody testing is used to diagnose autoimmune hepatitis (AIH), a cause of chronic liver disease (CLD). However, various autoantibodies are often detectable in patients with CLD due to other causes too. Since data on autoantibody prevalence in Indian patients with CLD are limited, we decided to undertake the current study. METHODS Patients with CLD with a known cause other than AIH and a separate group of patients with CLD in whom no cause could be identified were studied. Indirect immunofluorescence assays were used to detect anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver-kidney microsomal antibodies (anti-LKM). Serum dilutions tested were 1:80 for ANA and 1:40 for other autoantibodies. RESULTS Of the 175 patients with CLD of a known cause, 69 (39 %) had one or more autoantibodies, including ANA in 35 (20 %) patients and ASMA in 44 (25 %) patients. None had anti-LKM. The prevalence rates of any autoantibody, ANA and ASMA were similar in patients with CLD due to alcohol (34 %, 20 %, and 24 %, respectively), HCV infection (43 %, 20 %, and 26 %) and HBV infection (40 %, 18 %, and 25 %). The most common ANA pattern observed was speckled (29/35 patients), followed by nucleolar (5/35) and homogeneous (1/35). The ASMA titers did not exceed 1:80. The antibody prevalence rates were similar in patients with liver cirrhosis and chronic hepatitis, and in those with different disease severity. Serum IgG levels were similar in patients with and without detectable autoantibodies. Patients with no known cause of CLD (n = 50) had similar prevalence rates of autoantibodies, ANA or ASMA. CONCLUSION Autoantibodies were detected in a large proportion of patients with CLD, both cryptogenic and with known cause. Detection of autoantibodies in CLD does not necessarily indicate a diagnosis of AIH, and presence of homogenous pattern of ANA may be more relevant. Indiscriminate testing for autoantibodies in patients with CLD, especially those with a known cause, may not be warranted.
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Affiliation(s)
- Sunilbaran Daschakraborty
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
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15
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Autoimmune manifestations in viral hepatitis. Semin Immunopathol 2012; 35:73-85. [PMID: 23010889 DOI: 10.1007/s00281-012-0328-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 07/01/2012] [Indexed: 02/06/2023]
Abstract
Infections by the viruses responsible for hepatitis B, C and D are accompanied by a number of immunopathological manifestations. A link between infection and autoimmunity is particularly well documented for the hepatitis C virus. Immunopathological manifestations range from production of autoantibodies to overt autoimmune disease, including thyroiditis and autoimmune hepatitis, and to immune-complex-mediated disorders, including cryoglobulinaemia, glomerulonephritis and vasculitis. Several of these manifestations improve with successful antiviral treatment, directly incriminating the virus in their pathogenesis. Mechanisms considered responsible for hepatitis virus-related immunopathology, including molecular mimicry, impairment of regulatory T cells and activation of B lymphocytes, will be examined in this review.
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Hsieh MY, Dai CY, Lee LP, Huang JF, Chuang WL, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Yu ML. Antinuclear antibody titer and treatment response to peginterferon plus ribavirin for chronic hepatitis C patients. Kaohsiung J Med Sci 2012; 28:86-93. [PMID: 22313535 DOI: 10.1016/j.kjms.2011.10.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2010] [Accepted: 02/10/2011] [Indexed: 02/08/2023] Open
Abstract
Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon-α plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA <50 IU/mL throughout the follow-up period. Overall, 187 (77.0%) patients experienced a SVR. In the 105-patient HCV genotype non-1 group, patients with ANA titer ≥1:80 had a significantly lower SVR rate than those with ANA titer <1:80 (67.7% vs. 95.8%, respectively, p = 0.013). In contrast, in the 138-patient HCV genotype 1 group, the SVR rate did not differ between patients with and without ANA titer ≥1:80. Multivariate regressive analyses showed that ANA ≥1:80, age and HCV RNA levels were independent factors associated with SVR in HCV genotype non-1 patients; whereas HCV RNA levels and hepatic fibrosis were prognostic predictors of SVR in HCV genotype 1 patients. The frequencies of adverse events were similar between patients with and without ANA seropositivity. Peginterferon/ribavirin combination therapy is effective and safe in ANA-positive chronic hepatitis C patients. A high ANA titer was a negative prognostic factor for treatment response in HCV genotype non-1 patients.
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Affiliation(s)
- Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
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Covini G, Carcamo WC, Bredi E, von Mühlen CA, Colombo M, Chan EKL. Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C. Antivir Ther 2011; 17:805-11. [PMID: 22293655 DOI: 10.3851/imp1993] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2011] [Indexed: 12/24/2022]
Abstract
BACKGROUND Serum autoantibodies are frequently detected in patients with chronic HCV infection, reflecting the wide spectrum of immune reactions related to this virus. In the present study, a novel autoantibody to cytoplasmic rods and rings (RR) in chronic HCV patients was characterized. METHODS Sera from 75 previously untreated HCV patients were investigated by indirect immunofluorescence using HEp-2 cell substrate before and during pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. HEp-2 cells were cultured and fixed either following standard protocols or with the addition of RBV in culture medium. RESULTS In 15 out of 75 (20%) patients, analysis revealed the presence of antibodies to rod-like cytoplasmic structures ranging approximately 3-10 μm in length and rings approximately 2-5 μm in diameter. These RR structures became detectable in >95% of cells after addition of RBV in culture medium, whereas they were absent in untreated cells. Anti-RR antibodies were found in sera collected during PEG-IFN/RBV treatment only, but never detected before antiviral therapy nor in control groups. More importantly, these anti-RR antibodies were more often detected in non-responder/relapsers than in responder patients (33% versus 11%; P-value =0.037). CONCLUSIONS An RBV-induced autoantibody was identified to a new cytoplasmic autoantigenic structure developed in HCV patients after PEG-IFN/RBV and this same structure can be induced by RBV in in vitro culture. Owing to the onset of anti-RR antibodies in PEG-IFN/RBV-treated patients and their association with a treatment failure, studies are deemed necessary to clarify whether anti-RR plays a role in the response to PEG-IFN/RBV therapy.
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Affiliation(s)
- Giovanni Covini
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
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HIMOTO TAKASHI, YONEYAMA HIROHITO, DEGUCHI AKIHIRO, KUROKOHCHI KAZUTAKA, INUKAI MICHIO, MASUGATA HISASHI, GODA FUMINORI, SENDA SHOICHI, HABA REIJI, WATANABE SEISHIRO, NISHIOKA MIKIO, MASAKI TSUTOMU. Relationship between the production of autoantibodies to oxidized low-density lipoprotein and hepatic steatosis in patients with chronic hepatitis C. Exp Ther Med 2010. [DOI: 10.3892/etm_00000104] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Burdick LM, Somani N, Somani AK. Type I IFNs and their role in the development of autoimmune diseases. Expert Opin Drug Saf 2009; 8:459-72. [PMID: 19548860 DOI: 10.1517/14740330903066726] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Since their initial use in the 1980s, IFNs have become an essential component of the therapy for many diseases such as hepatitis and multiple sclerosis. Although they have been extremely useful in conditions that pose therapeutic challenges, complications associated with their use have been widely reported including emerging reports of several autoimmune diseases. Many of these reports have shed light on the pathogenesis of autoimmune disorders and helped to highlight not only the critical role of type I IFNs in defense against viral infections but also the pivotal role they occupy in the interface between innate and adaptive immunity. Many patients with autoimmune disease have increased responsiveness to type I IFNs (alpha/beta), and therapy with these cytokines has induced or unmasked autoimmune disease in many additional patients. OBJECTIVE The objective of this paper is to discuss the role of type I IFNs in autoimmunity. METHODS The literature regarding type I IFNs and autoimmunity was reviewed using the Medline database from 1950 to 2009. Search terms included 'interferon alpha' and 'autoimmune disease' and 'interferon beta' and 'autoimmune disease'. Case reports, case series, reviews and prospective studies were included in the analysis. RESULTS/CONCLUSIONS In the literature a variety of autoimmune disorders have reportedly been induced by the use of type I IFNs, being used, although these are primarily in the form of case reports and case series. Nevertheless, there is a growing body of molecular evidence to support the clinical association. The role of IFNs in the induction of autoimmunity is complex with interplay of many genetic and environmental factors that influence the balance between normal and aberrant immune responsiveness, ultimately leading to the observed clinical manifestations.
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Affiliation(s)
- Laura M Burdick
- Dermatology & Plastic Surgery Institute, Cleveland Clinic Health System, Department of Dermatology, 9500 Euclid Avenue, Desk A61, Cleveland, Ohio 44195, USA
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Williams MJ, Lawson A, Neal KR, Ryder SD, Irving WL. Autoantibodies in chronic hepatitis C virus infection and their association with disease profile. J Viral Hepat 2009; 16:325-31. [PMID: 19302340 DOI: 10.1111/j.1365-2893.2008.01035.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.
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Affiliation(s)
- M J Williams
- Wolfson Digestive Diseases Centre, Nottingham University Hosptial, Nottingham, UK.
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Chrétien P, Chousterman M, Alsamad IA, Ozenne V, Rosa I, Barrault C, Lons T, Hagège H. Non-organ-specific autoantibodies in chronic hepatitis C patients: Association with histological activity and fibrosis. J Autoimmun 2009; 32:201-5. [DOI: 10.1016/j.jaut.2009.02.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2009] [Accepted: 02/11/2009] [Indexed: 12/15/2022]
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Thyroid disorders and occurrence of nonorgan-specific autoantibodies (NOSA) in patients with chronic hepatitis C before and during antiviral induction therapy with consensus interferon (interferon alfacon-1). J Clin Gastroenterol 2009; 43:470-6. [PMID: 19247202 DOI: 10.1097/mcg.0b013e318184a470] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Thyroid disorders represent a common side effect of antiviral therapy in patients with chronic hepatitis C (CHC). However, there is strong evidence for a higher prevalence of thyroidal antibodies (TA) and nonorgan-specific autoantibodies (NOSA) even before interferon (IFN) administration. Here, we report for the first time on the distribution and occurrence of TA and NOSA before, during, and after treatment with daily highdosed IFN alfacon-1 [consensus IFN (CIFN)]. METHODS Thyrotropin (TSH) levels and antibodies to different autoantigens were analyzed in 217 patients with CHC (29.8% females) who were treated with CIFN induction therapy (27 or 18 mg q.d.). RESULTS Pretreatment abnormal TSH levels (TSH>3.0 mU/L or <0.4 mU/L) were detected in 15.6% and occurred significantly more often in females (24.6%; P=0.018). TA could be detected only in 2.6%, NOSA in up to 29.9% (47.4% females vs. 24.2% males). During CIFN induction therapy, low TSH levels were detected in 14.1% whereas elevated TSH levels occurred later (week 48) in up to 15.5%, again preferentially in females (42%, P=0.005). In 1.4% of all patients, treatment had to be discontinued because of symptomatic hyperthyroidism. TAs were detected in 10.5% (30.5% females) and NOSA up to 58% during CIFN treatment. CONCLUSIONS During CIFN induction therapy, alterations in TSH levels and an increased prevalence of TA and NOSA are quite common, especially in females. Clinically relevant symptoms occur, however, only in a small number (1.4%). Thus, treatment with daily and high-dose CIFN does not appear to increase the incidence of (severe) thyroidal or other autoimmune disorders compared with standard IFN in patients with CHC.
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Narciso-Schiavon JL, Freire FCF, Suarez MM, Ferrari MVO, Scanhola GQ, Schiavon LDL, Carvalho Filho RJD, Ferraz MLG, Silva AEB. Antinuclear antibody positivity in patients with chronic hepatitis C: clinically relevant or an epiphenomenon? Eur J Gastroenterol Hepatol 2009; 21:350-356. [PMID: 20611005 DOI: 10.1097/meg.0b013e3283089392] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Serum autoantibodies such as antinuclear antibody (ANA) are frequently detected in patients with chronic hepatitis C virus (HCV) infection, but its relevance is a matter of discussion. AIM To assess the association of ANA positivity with clinical and histological features, and with the outcome of antiviral therapy in patients with HCV infection. METHODS Baseline samples from patients with hepatitis C treated with interferon and ribavirin were tested for ANA positivity by indirect immunofluorescence. RESULTS The mean age was 48.3+/-11.1 years and 56% were men. Among 234 included patients, 22 patients (9.4%) were positive for ANA. These patients showed significantly higher median alanine aminotransferase level (3.52 vs. 2.39 x upper limit of normal, P=0.009) when compared with ANA-negative patients. Fibrosis stage and necroinflammatory grading were not influenced by ANA positivity. Sustained virological response (SVR) rates were similar between ANA-positive and ANA-negative patients (27 vs. 29%, P=0.882). Alanine aminotransferase flares (> or = 1.5-fold the baseline) during treatment were observed in 28 patients (12%), irrespective of the presence of ANA and without any clinical significance. CONCLUSION Among HCV patients, ANA positivity seems to represent an immunological epiphenomenon. It neither influences clinical, biochemical, and histological features of chronic hepatitis C nor predicts response to antiviral treatment.
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Egritas O, Sari S, Dalgic B, Vural C, Akyol G. Granulomatous hepatitis, perihepatic lymphadenopathies, and autoantibody positivity: an unusual association in a child with hepatitis C. Eur J Pediatr 2009; 168:275-279. [PMID: 18509673 DOI: 10.1007/s00431-008-0749-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2008] [Accepted: 04/22/2008] [Indexed: 10/22/2022]
Abstract
A 10-year-old boy with hepatitis C had granulomatous hepatitis (GH) at initial liver biopsy. He also had enlarged perihepatic lymph nodes and smooth muscle antibody (SMA) positivity. GH is a rare finding in hepatitis C virus (HCV) infection. Our patient is special since GH secondary to HCV infection was associated with both autoantibodies and multiple intraabdominal lymphadenopathies. After interferon (IFN) and ribavirin therapy, HCV RNA became negative, along with the resolution of hepatic granulomas (HG), lymphadenopathies, and SMA positivity. Although early virologic response was not achieved under IFN treatment, the therapy period was extended, contrary to routine practice, and resulted in a delayed response. We conclude that the usage of IFN for longer periods in GH-associated HCV infection might be promising.
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Affiliation(s)
- Odul Egritas
- Department of Pediatric Gastroenterology, Gazi University School of Medicine, Ankara, Turkey.
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25
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Hsieh MY, Dai CY, Lee LP, Huang JF, Tsai WC, Hou NJ, Lin ZY, Chen SC, Wang LY, Chang WY, Chuang WL, Yu ML. Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C. J Clin Pathol 2008; 61:333-337. [PMID: 17545561 DOI: 10.1136/jcp.2006.046276] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
AIMS Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to elucidate its clinical implications in virological and histological characteristics of CHC infection. METHODS A total of 614 CHC patients were enrolled in this prospective, hospital-based study. The serum levels of aspartate aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA level, and histological activity index scores for liver histopathology, were determined. RESULTS The prevalence of positive ANA (titre >1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012). Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs 49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA. Among 447 patients undergoing liver biopsy, those positive for ANA had a significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001) and a higher frequency of F3-4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than those negative for ANA. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels and age were significant factors related to positive ANA. CONCLUSION ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.
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Affiliation(s)
- M-Y Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Lin JH, Dutz JP, Sontheimer RD, Werth VP. Pathophysiology of Cutaneous Lupus Erythematosus. Clin Rev Allergy Immunol 2007; 33:85-106. [DOI: 10.1007/s12016-007-0031-x] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Gatselis NK, Georgiadou SP, Koukoulis GK, Tassopoulos N, Zachou K, Liaskos C, Hatzakis A, Dalekos GN. Clinical significance of organ- and non-organ-specific autoantibodies on the response to anti-viral treatment of patients with chronic hepatitis C. Aliment Pharmacol Ther 2006; 24:1563-73. [PMID: 17094775 DOI: 10.1111/j.1365-2036.2006.03165.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Development of organ- and non-organ-specific autoantibodies has been reported in hepatitis C virus patients treated with interferon-alpha plus/minus ribavirin. AIMS To address whether prevalence and the titre of gastric parietal autoantibodies and non-organ-specific autoantibody in hepatitis C virus-treated patients were affected by therapy, and if the development of these antibodies carries any clinical significance on the response to treatment, as few studies in adults have been strictly designed to address the above hypothesis. METHODS Samples at three time-points (baseline, end of treatment, end of follow-up) from 102 hepatitis C virus patients (39 sustained responders, 26 relapsers, 33 non-responders; four lost in follow-up) were studied for gastric parietal autoantibodies and/or non-organ-specific autoantibody by indirect immunofluorescence, commercial and in-house enzyme-linked immunosorbent assays. RESULTS Sustained virological and biochemical response was associated with antinuclear antibody absence (end of treatment or end of follow-up), decrease of smooth-muscle antibody titres during therapy and gastric parietal autoantibodies negativity at baseline. However, after multivariate analysis only antinuclear antibody positivity at the end of treatment and increase of smooth-muscle antibody titres were associated with worst treatment response, independently of known factors of worst treatment outcome. CONCLUSIONS We were able to demonstrate a negative correlation between the efficacy of anti-viral treatment for hepatitis C virus and the presence of antinuclear antibody and smooth-muscle antibody before treatment, or their increase during therapy.
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Affiliation(s)
- N K Gatselis
- Department of Medicine, Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
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Gehring S, Kullmer U, Koeppelmann S, Gerner P, Wintermeyer P, Wirth S. Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-alpha. World J Gastroenterol 2006; 12:5787-92. [PMID: 17007043 PMCID: PMC4100658 DOI: 10.3748/wjg.v12.i36.5787] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2006] [Revised: 08/05/2006] [Accepted: 08/14/2006] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity. METHODS We investigated the prevalence of auto-antibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-alpha) or combined treatment with interferon-alpha or peginterferon-alpha and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of anti-thyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined. RESULTS We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-alpha treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism. CONCLUSION Our data indicate a strong correlation between interferon-alpha treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.
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Affiliation(s)
- Stephan Gehring
- Children's Hospital, HELIOS Klinikum Wuppertal, Witten-Herdecke University, Heusnerstr. 40, D-42283 Wuppertal, Germany
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Elahi S, Buchanan RM, Attah-Poku S, Townsend HGG, Babiuk LA, Gerdts V. The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets. Infect Immun 2006; 74:2338-52. [PMID: 16552064 PMCID: PMC1418884 DOI: 10.1128/iai.74.4.2338-2352.2006] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 mug pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.
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Affiliation(s)
- Shokrollah Elahi
- Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
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Bogdanos DP, Mieli-Vergani G, Vergani D. Non-Organ-Specific Autoantibodies in Hepatitis C Virus Infection: Do They Matter? Clin Infect Dis 2005; 40:508-10. [PMID: 15712071 DOI: 10.1086/427293] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2004] [Accepted: 10/19/2004] [Indexed: 12/20/2022] Open
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Muratori P, Muratori L, Guidi M, Granito A, Susca M, Lenzi M, Bianchi FB. Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C. Clin Infect Dis 2005; 40:501-507. [PMID: 15712070 DOI: 10.1086/427285] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2004] [Accepted: 09/14/2004] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients. METHODS A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment. RESULTS Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively). CONCLUSIONS Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is less likely in those infected with HCV-1.
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Affiliation(s)
- Paolo Muratori
- Department of Internal Medicine, Cardioangiology, Alma Mater Studiorum-University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy.
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Gatselis NK, Georgiadou SP, Tassopoulos N, Zachou K, Liaskos C, Hatzakis A, Dalekos GN. Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study. World J Gastroenterol 2005; 11:482-7. [PMID: 15641130 PMCID: PMC4250795 DOI: 10.3748/wjg.v11.i4.482] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients.
METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs.
RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy.
CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- α may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.
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Affiliation(s)
- Nikolaos K Gatselis
- Department of Internal Medicine, Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
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