Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormalities in multiple sclerosis (P2.214)

OBJECTIVE This study aimed to investigate whether the rates of oligoclonal IgG band (OCB) positivity and an elevated IgG index in Japanese multiple sclerosis (MS) patients are different between the Japanese islands of Hokkaido and Kyushu, which exhibit a latitude difference of approximately 10°. We also investigated whether any differences in OCB positivity and the elevated IgG index in MS patients from these islands were affected by HLA-DRB1*04:05 and *15:01 alleles. BACKGROUND Although a small but statistically significant north-south gradient of MS prevalence rates is seen in Japan, it is unclear whether the prevalence of OCBs in MS differs between the northern and southern regions of Japan. DESIGN/METHODS This study included 180 MS patients from Hokkaido (a northern region) and 184 patients from Kyushu (a southern region). The IgG index was considered increased if it was >0.658. The presence of cerebrospinal fluid (CSF) OCBs and/or an increased IgG index were defined as positive CSF findings. RESULTS Positive CSF findings and OCB positivity were significantly more frequent in MS patients from Hokkaido than in those from Kyushu (73.9[percnt] vs. 43.5[percnt] for CSF positivity, 63.3[percnt] vs. 41.4[percnt] for OCB positivity; p < 0.0001 for both). Logistic regression analysis revealed that after adjusting for covariates possibly related to abnormal CSF IgG production, Hokkaido showed odds ratios of 4.08 and 2.57 for positive CSF findings and OCB positivity, respectively, while HLA-DRB1*04:05 showed odds ratios of 0.36 and 0.30, respectively. CONCLUSIONS A north-south gradient in OCB positivity in MS patients may be common in Japan and Western countries. However, OCB positivity in Japan, even in northern Japan, which shows a high prevalence of OCB positivity, is lower than that observed in Western countries. The HLA-DRB1*04:05 allele is protective for abnormal IgG production in Japanese MS patients, regardless of latitude. Disclosure: Dr. Niino has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Asahi Kasei Kuraray Medical Co., Ltd., and Novartis. Dr. Sato has nothing to disclose. Dr. Fukazawa has received personal compensation for activities with Bayer Schering, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, and Novartis. Dr. Yoshimura has nothing to disclose. Dr. Hisahara has nothing to disclose. Dr. Matsushita has received personal compensation for activities with Bayer Schering Pharma, Pfizer Inc., and Mitsubishi Tanabe Pharma Corporation as a speaker. Dr. Isobe has received research support from the Uehara Memorial Foundation. Dr. Yoshida has nothing to disclose. Dr. Houzen has received personal compensation for activities with Biogen Idec, Novartis Pharmaceuticals, and Mitsubishi Tanabe Pharma as a scientific advisory board member. Dr. Miyazaki has received personal compensation for activities with Novartis and Biogen Idec. Dr. Shimohama has nothing to disclose. Dr. Kikuchi has received personal compensation for activities with Novartis, Boehringer Ingelheim, Kyowa Hakko Kirin, Dainippon Sumitomo Pharma, and FP Pharmaceutical Corporation. Dr. Kira has received personal compensation for activities with Biogen Idec.