HLA‐DP ANTIGENS AND HTLV‐1 ANTIBODY STATUS AMONG JAPANESE WITH MULTIPLE SCLEROSIS: EVIDENCE FOR AN INCREASED FREQUENCY OF HLA‐DPw4.

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Abstract
Previously, an association between multiple sclerosis (MS) and HLA-DPw4 has been reported in Scandinavians. In the present study, the distribution of HLA-DP antigens was studied in 34 Japanese MS patients, a11 of whom fulfilled the criteria for definite MS. HLA-DP typings for DPwl through w6 and the local specificity, CDP-HEI, were performed using the primed lymphocyte typing (PLT) technique. In addition, the patients were typed for a DR2 +, Dw2 +/Dw12–related, PLT defined specificity. The distribution of DPw1-w5 in 121 healthy, unrelated Japanese controls were from Nishimura et al., 1984; Nishimura, personal communication). Sera from all 34 patients and 38 controls (both from the HTLV-1 non-endemic, Kyoto region) were examined for the presence of HTLV-1 reacting antibodies by a highly sensitive radioimmuno assay (RIA) using two sources of HTLV-1 antigens, namely total crude protein preparations from disrupted HTLV-1 virions and affinity purified p24 HTLV-1 core proteins. The frequency of DPw4 was significantly increased to 35.3% in Japanese MS patients compared to 16.5% in controls (Relative Risk, RR = 2.8, p = 1.9 × 10−2). 41.6% of the MS patients gave clear typing responses with a PLT reagent which recognized a Dw2+ related specificity, which is higher than the frequency of Dw2 (6.8%) in Japanese. Fourteen of the 34 patient sera contrasting to none of the sera from 38 controls contained antibodies of IgG and/or IgM subclasses reacting with the HTLV-1 derived antigens. This difference is highly significant (P < 1 × 10−5). However, there was no association between DP or Dw2 phenotypes and antibody status. These data provide evidence that genes within (or closely linked to) the HLA-DP region confer susceptibility to MS in two genetically different ethnic groups: Japanese and Scandinavians.