Autoantibodies to apolipoprotein A-I in hepatitis C virus infection: a role in disease progression?

Simon H. Bridge ^1* Sabrina Pagano ² John K Lodge ^3* Isaac T. Shawa ⁴ Paula Marin-Crespo ¹ Matthew Cramp ⁵ David A. Sheridan ^4* Simon D. Taylor-Robinson ^6* Nicolas Vuilleumier ² R Dermot Neely ^7* Margaret F. Bassendine ^8*

• ¹ Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom
• ² Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Geneva, Switzerland
• ³ School of Human Sciences, London Metropolitan University, London, United Kingdom
• ⁴ Faculty of Health, Peninsula Medical School, University of Plymouth, Plymouth, England, United Kingdom
• ⁵ Peninsula Medical School, Faculty of Medicine and Dentistry, University of Plymouth, Plymouth, England, United Kingdom
• ⁶ Department of Surgery and Cancer, Imperial College London, London, United Kingdom
• ⁷ Department of Blood Sciences, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
• ⁸ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, England, United Kingdom

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 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 non-viraemic individuals (25 SR and 89 SVR) were assayed for AAA-I and lipoproteins. AUC were calculated for AAA-I and HDL-related parameters and used for predicting 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 were 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 for predicting cirrhosis was 0.72 (p <0.001), 0.65 (p = 0.01) and 0.64 (p = 0.02). After 48 hours 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 in the presence of 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.