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HLA-DPB1*0501 is not uniquely associated with opticospinal multiple sclerosis in Japanese patients. Important role of DPB1*0301

Hokuyukai Neurology Hospital, Niju-Yon-Ken 2-2-4-30, Nishi-ku, Sapporo 063-0802, Japan, Nishimaruyama Hospital, Maruyama-Nishimachi 4-7-25, Chuo-ku, Sapporo 064-8557, Japan, fukazawa{at}my.email.ne.jp

S Kikuchi

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060- 8638, Japan

R Miyagishi

Nishimaruyama Hospital, Maruyama-Nishimachi 4-7-25, Chuo-ku, Sapporo 064-8557, Japan

Y Miyazaki

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060- 8638, Japan

I Yabe

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060- 8638, Japan

T Hamada

Hokuyukai Neurology Hospital, Niju-Yon-Ken 2-2-4-30, Nishi-ku, Sapporo 063-0802, Japan

H Sasaki

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060- 8638, Japan

Apart from its unique lesion distribution pattern, the opticospinal form of multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the diagnostic criteria of MS. OSMS has been suggested to be strongly associated with HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and non-OSMS (82%) were similar, but both were higher than in the controls (66%). In DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL) were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22 out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS patients. Our findings indicate that DPB1*0501 plays an important role in the development of MS in general, but not in OSMS. The strong association of DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant to the development of periventricular lesions in Japanese patients with MS.

Key Words: Devic’s disease • HLA-DPB1 • Japanese • multiple sclerosis • neuromyelitis optica • opticospinal MS

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