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, DRβ1 and DQβ1. Results: Higher allele frequencies of HLA-DRβ1*08 and DQβ1*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 DRβ1*0801 were positive for the DQβ1*0402 allele, delta SCORE=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRβ1*08 and DQβ1*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.