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Persistently elevated abnormal B‐cell subpopulations and anti‐core antibodies in patients co‐infected with HIV/HCV who relapse
Author(s) -
Kohli Anita,
Funk Emily,
Burbelo Peter,
Barrett Lisa,
Meissner Eric G.,
Santich Brian,
Shaffer Ashton,
Johl Jessica,
Sidharthan Sreetha,
Moir Susan,
Kottilil Shyam,
Fauci Anthony S.
Publication year - 2015
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24089
Subject(s) - viremia , medicine , immunology , antibody , hepatitis c virus , subclinical infection , virology , viral load , titer , hepatitis c , hepacivirus , peripheral blood mononuclear cell , virus , biology , in vitro , biochemistry
Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency virus (HIV) and HCV is associated with modest rates of sustained virologic response (SVR) and an increased rate of relapse when compared to HCV monoinfected patients. As patients who attain SVR and patients who relapse are clinically indistinguishable during treatment, where both groups have fully suppressed HCV viral load, it has not been possible to identify in advance those who will relapse. Biomarkers that may distinguish patients with differential treatment response may be clinically useful and provide insight into mechanisms of relapse. In this retrospective study, serum and PBMCs were obtained from 41 HIV/HCV co‐infected patients and 17 healthy volunteers. Changes in antibody titers to various regions of the HCV proteome during treatment for HCV were determined using a novel luciferase immunoprecipitation assay. Changes in B‐cell subtypes in patients with differential treatment response as well as healthy volunteers were compared. This study demonstrates that elevated anti‐HCV core antibody titers persisted during HCV treatment in patients who relapsed when compared to those who attained SVR. Furthermore, characterization of B cells in patients who relapsed demonstrated an abnormal B‐cell phenotype distribution characterized by elevated frequencies of exhausted B cells among relapsers at baseline, which persisted despite suppression of HCV viremia at 24 weeks, along with increased frequencies of plasmablasts. These data suggest that anti‐HCV specific B cells may be responding to ongoing subclinical HCV replication in patients who will relapse. J. Med. Virol. 87:544–552, 2015 . © 2015 Wiley Periodicals, Inc.