PRIMARY BILIARY-CIRRHOSIS - CONTRIBUTION OF HLA CLASS-II ALLELE DR8

Primary biliary cirrhosis is a chronic cholestatic disease of unknown aetiology which predominantly affects middle-aged women. It is thought to be autoimmune in nature, but unlike many autoimmune diseases no cl ear HLA association has been described. Several studies have suggested conflicting associations with HLA class II, although a DR8 associatio n is most frequently described. To test the hypothesis that primary bi liary cirrhosis is associated with a certain HLA class II locus we gen otyped 130 patients with the disease from the north-east region of Eng land and 363 local healthy controls. HLA-DRB1 and confirmatory DQA and DQB genotypes were determined by TaqI restriction fragment DNA length polymorphism analysis. In addition, a polymerase chain reaction techn ique (double ARMS) was used to investigate the DRB3 locus (DR52) in 98 primary biliary cirrhosis patients and 107 local controls. We found a n increased frequency of HLA-DR8 (18.5% vs 9.2%, p<0.005, relative ris k of 2.0 [1.3-3.1]) in the primary biliary cirrhosis group. HLA-DR8-po sitive primary biliary cirrhosis patients had a higher serum bilirubin level (p = 0.03) than DR8-negative patients. There was no difference in the DR52 frequencies and no association with markers of disease sev erity. These results support earlier serological findings, although th e association between primary biliary cirrhosis and DR8 is weaker than previously described. In addition, DR8-positivity may identify a clin ical subgroup with a worse prognosis.