Association between an MHC Class II Allele and Clearance of Hepatitis B Virus in the Gambia
Mark R. Thursz, M.R.C.P., Dominic Kwiatkowski, M.R.C.P., Catherine E.M. Allsopp, Ph.D., Brian M. Greenwood, F.R.C.P., Howard C. Thomas, Ph.D., and Adrian V.S. Hill, D.M.
Background The course of hepatitis B virus (HBV) infection doesnot appear to be determined by variations in viral virulenceand may be influenced by the host immune response. We studiedthe distribution of human leukocyte antigens in children andadult men in the Gambia who spontaneously recovered from HBVinfection as compared with the distribution of these antigensin subjects with persistent infection.
Methods In a two-stage, case –control study, we analyzedthe frequency of MHC class I antigens and class II haplotypesin subjects with either transient or persistent HBV infection.MHC class I typing was performed by microlymphocytotoxicityassays. MHC class II typing was performed with analysis of restriction-fragment–lengthpolymorphisms (RFLPs), supplemented by other techniques.
Results In the first stage (the study of children up to theage of 10 years), the RFLP pattern 25-1, which includes theclass II allele HLA-DRB1*1302, was found in 58 of 218 subjectswith transient HBV infection (26.6 percent) and 30 of 185 subjectswith persistent infection (16.2 percent) (relative risk of carryingthe 25-1 pattern in the persistently infected group as comparedwith the transiently infected group, 0.53; 95 percent confidenceinterval, 0.32 to 0.90; P = 0.012). In the second stage (thestudy of adults), HLA-DRB1*1302 was found in 50 of 195 subjectswith transient HBV infection (25.6 percent) and in 3 of 40 subjectswith persistent infection (7.5 percent) (relative risk, 0.24;95 percent confidence interval, 0.04 to 0.80; P = 0.012). TheRFLP pattern 13-2, which includes the class II allele DRB1*1301,was less frequent in children with persistent infection thanin those with transient infection, an association that was neitherconfirmed nor excluded by the data on adults. Possible associationswith HLA class I antigens found in children were not supportedby the data on adults.
Conclusions The MHC class II allele DRB1*1302 was associatedwith protection against persistent HBV infection among bothchildren and adults in the Gambia.
Source Information
From the Hepatology Unit, Academic Department of Medicine, St. Mary's Hospital Medical School, Imperial College, London (M.R.T., H.C.T.); the Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (D.K., C.E.M.A., A.V.S.H.); and the Medical Research Council Laboratories, Fajara, the Gambia (B.M.G., A.V.S.H.).
Address reprint requests to Dr. Thursz at the Department of Medicine, St. Mary's Hospital Medical School, London W2 1NY, United Kingdom.
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