Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis

Background/Aims: An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls. Methods: Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRbeta1 and DQbeta1. Results: Higher allele frequencies of HLA-DRbeta1*08 and DQbeta1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR) = 3.3, global P = 0.03 and 14.4% vs. 6.5%, OR = 2.6, global P = 0.002). All patients positive for DRbeta1*0801 were positive for the DQbeta1*0402 allele, delta score = 22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRbeta1*08 and DQbeta1*04 was 0%, significantly different from the AMA-positive patients (P = 0.05, P = 0.05). Conclusions: AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science BA. All rights reserved.