title: HLA-Cw*04 and hepatitis C virus persistence.
abstract: In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, USA. cthio@jhmi.edu
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: David
authors.initials: D
authors.lastname: Vlahov
authors.forename: Kenrad E
authors.initials: KE
authors.lastname: Nelson
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Hilgartner
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Peter
authors.initials: P
authors.lastname: Karacki
authors.forename: Jacquie
authors.initials: J
authors.lastname: Astemborski
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D008040:Genetic Linkage; D015236:HLA-C Antigens / Q000032:analysis / Q000235:genetics*; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D016017:Odds Ratio
chemical_list: D015236:HLA-C Antigens