Simon H Bridge, Sabrina Pagano, John K Lodge, Isaac T Shawa, Paula Marin-Crespo, Matthew E Cramp, David A Sheridan, Simon D Taylor-Robinson, Nicolas Vuilleumier, R Dermot G Neely, Margaret F Bassendine
{"title":"丙型肝炎病毒感染的载脂蛋白a - i自身抗体：在疾病进展中的作用？","authors":"Simon H Bridge, Sabrina Pagano, John K Lodge, Isaac T Shawa, Paula Marin-Crespo, Matthew E Cramp, David A Sheridan, Simon D Taylor-Robinson, Nicolas Vuilleumier, R Dermot G Neely, Margaret F Bassendine","doi":"10.3389/fimmu.2025.1461041","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic HCV (CHC) infection is associated with autoimmunity. IgG autoantibodies to apolipoprotein A-I (AAA-I) predict all-cause mortality. We evaluated AAA-I in CHC patients and in those who were not viraemic, either because of spontaneous resolution (SR) of infection or HCV clearance following sustained virological response (SVR) after interferon therapy. We limited the study to HCV genotypes 1 and 3, the dominant HCV genotypes circulating in the UK.</p><p><strong>Methods: </strong>Serum samples from 126 CHC patients and 114 nonviraemic individuals (25 SR and 89 SVR) were assayed for AAA-I and lipoproteins. AUC was calculated for AAA-I and HDL-related parameters and used to predict cirrhosis. Fibronectin (FN) and FN-mRNA were measured in human hepatic stellate cells (LX-2) in the presence or absence of AAA-I.</p><p><strong>Results: </strong>AAA-I was found in 47% of patients with CHC, 37% of SVR patients, and 16% of SR individuals (CHC vs. SR, <i>p</i> = 0.004). AAA-I levels in CHC patients were higher in those with cirrhosis (<i>p</i> = 0.0003). The AUC for AAA-I, apoA-I, and HDL-C in predicting cirrhosis was 0.72 (<i>p</i> < 0.001), 0.65 (<i>p</i> = 0.01), and 0.64 (<i>p</i> = 0.02). After 48 h in the presence of AAA-I, LX-2 cells showed an 80% increase in FN-mRNA compared to the LX-2/IgG control (<i>p</i> = 0.028) and higher levels of FN (<i>p</i> = 0.0016).</p><p><strong>Conclusions: </strong>CHC is often associated with AAA-I, and these can persist after SVR. AAA-I is a robust predictor of cirrhosis in CHC infection. LX-2 cells exposed to AAA-I showed increased FN. Further studies are warranted to define the role of AAA-I in promoting not only viral persistence but also fibrosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1461041"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965114/pdf/","citationCount":"0","resultStr":"{\"title\":\"Autoantibodies to apolipoprotein A-I in hepatitis C virus infection: a role in disease progression?\",\"authors\":\"Simon H Bridge, Sabrina Pagano, John K Lodge, Isaac T Shawa, Paula Marin-Crespo, Matthew E Cramp, David A Sheridan, Simon D Taylor-Robinson, Nicolas Vuilleumier, R Dermot G Neely, Margaret F Bassendine\",\"doi\":\"10.3389/fimmu.2025.1461041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic HCV (CHC) infection is associated with autoimmunity. IgG autoantibodies to apolipoprotein A-I (AAA-I) predict all-cause mortality. We evaluated AAA-I in CHC patients and in those who were not viraemic, either because of spontaneous resolution (SR) of infection or HCV clearance following sustained virological response (SVR) after interferon therapy. We limited the study to HCV genotypes 1 and 3, the dominant HCV genotypes circulating in the UK.</p><p><strong>Methods: </strong>Serum samples from 126 CHC patients and 114 nonviraemic individuals (25 SR and 89 SVR) were assayed for AAA-I and lipoproteins. AUC was calculated for AAA-I and HDL-related parameters and used to predict cirrhosis. Fibronectin (FN) and FN-mRNA were measured in human hepatic stellate cells (LX-2) in the presence or absence of AAA-I.</p><p><strong>Results: </strong>AAA-I was found in 47% of patients with CHC, 37% of SVR patients, and 16% of SR individuals (CHC vs. SR, <i>p</i> = 0.004). AAA-I levels in CHC patients were higher in those with cirrhosis (<i>p</i> = 0.0003). The AUC for AAA-I, apoA-I, and HDL-C in predicting cirrhosis was 0.72 (<i>p</i> < 0.001), 0.65 (<i>p</i> = 0.01), and 0.64 (<i>p</i> = 0.02). After 48 h in the presence of AAA-I, LX-2 cells showed an 80% increase in FN-mRNA compared to the LX-2/IgG control (<i>p</i> = 0.028) and higher levels of FN (<i>p</i> = 0.0016).</p><p><strong>Conclusions: </strong>CHC is often associated with AAA-I, and these can persist after SVR. AAA-I is a robust predictor of cirrhosis in CHC infection. LX-2 cells exposed to AAA-I showed increased FN. Further studies are warranted to define the role of AAA-I in promoting not only viral persistence but also fibrosis.</p>\",\"PeriodicalId\":12622,\"journal\":{\"name\":\"Frontiers in Immunology\",\"volume\":\"16 \",\"pages\":\"1461041\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965114/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fimmu.2025.1461041\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1461041","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Autoantibodies to apolipoprotein A-I in hepatitis C virus infection: a role in disease progression?
Background: Chronic HCV (CHC) infection is associated with autoimmunity. IgG autoantibodies to apolipoprotein A-I (AAA-I) predict all-cause mortality. We evaluated AAA-I in CHC patients and in those who were not viraemic, either because of spontaneous resolution (SR) of infection or HCV clearance following sustained virological response (SVR) after interferon therapy. We limited the study to HCV genotypes 1 and 3, the dominant HCV genotypes circulating in the UK.
Methods: Serum samples from 126 CHC patients and 114 nonviraemic individuals (25 SR and 89 SVR) were assayed for AAA-I and lipoproteins. AUC was calculated for AAA-I and HDL-related parameters and used to predict cirrhosis. Fibronectin (FN) and FN-mRNA were measured in human hepatic stellate cells (LX-2) in the presence or absence of AAA-I.
Results: AAA-I was found in 47% of patients with CHC, 37% of SVR patients, and 16% of SR individuals (CHC vs. SR, p = 0.004). AAA-I levels in CHC patients were higher in those with cirrhosis (p = 0.0003). The AUC for AAA-I, apoA-I, and HDL-C in predicting cirrhosis was 0.72 (p < 0.001), 0.65 (p = 0.01), and 0.64 (p = 0.02). After 48 h in the presence of AAA-I, LX-2 cells showed an 80% increase in FN-mRNA compared to the LX-2/IgG control (p = 0.028) and higher levels of FN (p = 0.0016).
Conclusions: CHC is often associated with AAA-I, and these can persist after SVR. AAA-I is a robust predictor of cirrhosis in CHC infection. LX-2 cells exposed to AAA-I showed increased FN. Further studies are warranted to define the role of AAA-I in promoting not only viral persistence but also fibrosis.
期刊介绍：
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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