B cell receptor repertoire analysis in HCV chronically infected patients and Primary Sjogren’s Syndrome

Authors

• J Pardoe
• A Henning
• B Warner
• V De Giorgi

Abstract

Chronic infection of hepatitis C virus (HCV) is a worldwide health issue affecting an estimated 58 million people. Primarily hepatotropic, HCV can also result in extrahepatic manifestations including sicca syndrome with commonly reported symptoms of dry eye and mouth which subjectively improve after antiviral treatment. These symptoms mirror those of primary Sjogren’s syndrome (pSS), a systemic autoimmune disease characterized by infiltration of lymphocytes in salivary and lachrymal glands. Both individuals with chronic HCV and those with pSS are at an increased risk of developing B cell lymphomas. In these associated lymphomas, expansion of monoclonal B cells has been shown. We sought to investigate if clonal expansion may also occur in the periphery of HCV+ and pSS patients and determine if the BCR repertoire is affected in HCV+ individuals based on sicca status or antiviral treatment. B cells were isolated from PBMC of HCV+ patients reporting sicca symptoms (n=6), HCV+ patients without sicca symptoms (n=8), pSS patients (n=5), and healthy donors (n=4). HCV+ patient B cells were collected before and after treatment with direct acting antivirals (DAAs). Targeted sequencing of the full V(D)J region was performed on all samples for IgK, IgL, IgG, and IgM. We report in-depth characterization of the BCR repertoires of each group, including gene family usage and any evidence of clonal expansion. Preliminary analysis suggests no significant differences in gene family usage or diversity between the groups or in HCV+ individuals following DAA treatment. One pSS patient showed evidence of clonal expansion in IgK and IgM.

Scientific Focus Area: Immunology

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