查看文章

Susceptibility to autoimmune hepatitis in white patients is associated with the human leukocyte antigen class II antigens DR3 and DR4. To analyze the molecular basis of these associations, we used oligonucleotide probes to determine the DRB, DQA and DQB hypervariable nucleotide sequences in 119 patients with autoimmune hepatitis and 177 matched controls. DRB3* 0101, which encodes DR52a, predisposed patients most strongly to the disease. It was present in 58% of patients and 25% of controls (corrected P< 0.000005), whereas DQA1* 0101 and 0102 conferred protection in males only. The DR4 subtype, DRB1* 0401, was raised in the DRB3* 0101-negative patients; 81% possessed either DRB3* 0101 or DRB1* 0401, compared with 42 of controls (corrected P< 0.0000001). These alleles encode the amino acid sequence Leu-Leu-Glu-Gln-Lys-Arg at positions 67 to 72 of the DRβ polypeptide, which …