New HLA DNA polymorphisms associated with rheumatoid arthritis.

Studies of restriction enzyme fragment length polymorphisms (RFLP) have further clarified two DNA polymorphisms detected in DR4 positive individuals with a DQ beta probe. These patterns have been designated DQ beta omega, characterized in the Dw4 homozygous typing cell (HTC) BM14 and DQ beta phi, characterized in the Dw4 HTC MCF, and so do not correspond with different Dw types. These patterns clearly segregate in families with HLA haplotypes. We suggest that omega and phi may be polymorphisms of the DX beta gene. The previously reported DX alpha polymorphisms U and L were found with all DR types and in association with DQ beta omega (U) and DQ beta phi(L). In addition DQ beta phi was found to be strongly associated with TA10 positively (a subdivision of DQw3) although this association was not absolute. Associations between RFLP and other HLA Class II and I antigens seen in DR4 patients and DR4 controls suggest the existence of at least two preferential allelic associations (PAA), one containing omega/U and the other phi/L. PAA1: DX alpha U-DQ beta omega-TA10 negative-DQw3-Dw4-DR4----Bw62-Bw6-Cw3-A2 PAA2: DX alpha L-DQ beta phi-TA10 positive-DQw3-Dw4-DR4----B44-Bw4-Cw3-A2 The frequency of the omega pattern was higher, although not significantly in the RA patients compared with controls. However, a significantly higher frequency of omega was found in RA patients with extra-articular manifestations (EA) compared (a) with controls (p less than 0.04) and (h) with those patients without EA (p less than 0.05). In addition the frequency of phi was significantly higher in RA patients with nodules and/or erosions (N/ER) compared with patients without these features (p less than 0.008). When cumulative scores were assigned to patients after assessing the number of components fulfilled for each PAA, PAA1 appeared to be pronounced in patients with EA and PAA2 in patients with N/ER. The frequency of a previously reported DQ beta T6 band found with the enzyme Taq 1 and DQ-beta probe was found at a higher frequency in RA patients compared with controls. In addition a significantly higher frequency of this band was found in female RA patients compared to males.