title: Persistently elevated abnormal B-cell subpopulations and anti-core antibodies in patients co-infected with HIV/HCV who relapse.
abstract: 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.
authors.affiliation: Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.forename: Emily
authors.initials: E
authors.lastname: Funk
authors.forename: Peter
authors.initials: P
authors.lastname: Burbelo
authors.forename: Lisa
authors.initials: L
authors.lastname: Barrett
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.forename: Brian
authors.initials: B
authors.lastname: Santich
authors.forename: Ashton
authors.initials: A
authors.lastname: Shaffer
authors.forename: Jessica
authors.initials: J
authors.lastname: Johl
authors.forename: Sreetha
authors.initials: S
authors.lastname: Sidharthan
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D015415:Biomarkers; D018937:Hepatitis C Antibodies; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus
keywords: B cell; HCV; HIV; LIPS; hepatitis C core antibody