Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis

✍ Scribed by Derek G. Doherty; Peter T. Donaldson; James A. Underhill; J. Mark Farrant; Ann Duthie; Giorgina Mieli-Vergani; Ian G. McFarlane; Philip J. Johnson; Adrian L. W. F. Eddleston; Alex P. Mowat; Dr. Roger Williams

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 809 KB
• Volume: 19
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840190311

✦ Synopsis

Susceptibility to autoimmune hepatitis in white patients is associated with the human leukocyte antigen class I1 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 DQAl*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 DRf3 polypeptide, which was present in 94% of patients and 64% of controls (corrected P < 0.000001) and in all patients who tested positive for autoantibodies to the hepatic asialoglycoprotein receptor. The patients with DFlB1*0401 had less severe disease, relapsed less frequently and were first seen significantly later inlife than those patients with DRB3*0101;