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Journal of Virology, November 2003, p. 12083-12087, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12083-12087.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Comprehensive Analysis of Class I and Class II HLA Antigens and Chronic Hepatitis B Virus Infection

Chloe L. Thio,1* David L. Thomas,1 Peter Karacki,1 Xiaojiang Gao,2 Darlene Marti,2 Richard A. Kaslow,3 James J. Goedert,4 Margaret Hilgartner,5 Steffanie A. Strathdee,6 Priya Duggal,6 Stephen J. O'Brien,2 Jacquie Astemborski,1 and Mary Carrington2

Department of Medicine,1 Department of Epidemiology, Johns Hopkins Medical Institutions, Baltimore,6 Laboratory of Genomic Diversity, National Cancer Institute, Frederick,2 Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland,4 Department of Epidemiology, University of Alabama, Birmingham, Alabama,3 Department of Pediatrics, New York Presbyterian Hospital-Cornell Medical Center, New York, New York5

Received 12 February 2003/ Accepted 9 August 2003

Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.

* Corresponding author. Mailing address: Johns Hopkins University, 1503 E. Jefferson St., Baltimore, MD 21231-1001. Phone: (410) 955-0349. Fax: (410) 614-7564. E-mail: cthio{at}jhmi.edu.

Journal of Virology, November 2003, p. 12083-12087, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12083-12087.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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