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.