Strong Linkage Disequilibrium between HLA—Dw2 and BfS in Multiple Sclerosis and in the Normal Population

Abstract

An increased frequency of the S allele of Properdin factor B (BfS) was found amongst 162 patients with multiple sclerosis (MS) compared with 470 normal controls. This increase was shown to be due to a strong linkage disequilibrium (LD) between BfS and HLA—Dw2 in 77 patients typed for both systems (Δ= 3.84%, P= .0002). The same LD was demonstrated amongst 100 normal controls (Δ= 2.24%, P= .0049) and 31 patients with idiopathic demyelination of the peripheral nervous system (IDPN). A total of 70 haplotypes with HLA-Dw2 were encountered (40 MS, seven IDPN and 23 normal controls) and all contained BfS. In the MS patient group, a much weaker association was noted between BfS and HLA—B7 suggesting either that the Bf locus is much closer to the HLA—D than the HLA—B locus or (and) that HLA-D and Bf products selectively interact (perhaps on the surface of B lymphocytes) with evolutionary advantage or disadvantage resulting from certain allelic combinations. Strong associations between BfS₁ and HLA—Bw21 (P= .0000) and BfF₁ and HLA—B18 (P= .0001), both previously reported, were confirmed in the current study. No increase in the frequency of a glyoxalase (GLO) allele was found amongst the MS patients and no LD was encountered between HLA—Dw2 and a GLO allele. The possibility that the HLA—Dw2, BfS disequilibrium has resulted from a selective advantage conferred on the general community but at the expense of increasing susceptibility to MS should be considered.