HLA‐DR4 associated Dw types in rheumatoid arthritis

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Abstract
Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p < 0.001) and Dw14 (22.8% vs. 2.1% RR = 13.9 p < 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p < 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all R4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data, Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3, BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 2.76% X2 = 2.1 p = ns). By using a DQ-beta probe and a range of restriction enzymes, the DNA of Dw typed DR4 positive RA patients and controls was classified into either the omega or phi restriction fragment length polymorphism (RFLP) patterns. No obvious inclination towards one of these patterns was observed with Dw4 or Dw14. However, when haplotypes were considered, the majority of the B44-DR4-Dw4 haplotypes were the phi pattern, whereas the Bw62-DR4-Dw4 and the Bw60-DR4-Dw14 haplotypes were omega. There was an indication that Dw10 is associated wtih omega and Dw13 with phi.