POSITIVE AND NEGATIVE ASSOCIATIONS OF DISTINCT HLA-DR2 SUBTYPES WITH ULCERATIVE-COLITIS (UC)

In UC, as in many other diseases with a suspected autoimmune etiology or pathogenesis, an association with certain HLA class II specificitie s has been investigated. In the Japanese, several studies have shown a positive association with DR2, but in Caucasian populations the resul ts are conflicting. Therefore we undertook a study of HLA class II gen e association with UC in a large group of white Madrid patients and et hnically matched controls, using molecular biology techniques to inves tigate whether any allelic subspecificity within the HLA-DR2 group is associated with susceptibility to or protection against UC. Patients w ith ulcerative colitis (n=107) and 200 controls were typed using molec ular, DNA-based techniques for HLA-DRB1, DQA1 and DQB1 alleles. Those HLA-DR2(+) were then specifically typed for the individual alleles wit hin the HLA-DR2 group. We observed a positive association with HLA-DR1 5 (P=0.021) and its subtype DRB11501 (P=0.018). HLA-DRB1*1502 was als o increased, although its frequency both in patients and controls was very low. When the HLA-DR2(+) population was studied, HLA-DRB11601 wa s significantly decreased in patients (P=0.026). Both HLA-DR3 (P=0.002 ) and HLA-DQB102 (P=0.001) were also negatively associated with the d isease, the latter especially with pancolitis. Therefore, HLA class II association with UC is complex, and separate alleles confer either su sceptibility or resistance. Conflicting results with HLA-DR2 appear to be due to the presence in this group of both positively associated (H LA-DRB11501 and DRB1*1502) and negatively associated (HLA-DRB1*1601) subspecificities. Moreover, HLA-DR3 and HLA-DQB102 are associated neg atively.