Distinct Genetic and Infectious Profiles between Multiple Sclerosis and Neuromyelitis Optica in Japanese Patients (P05.122)

Abstract

Objective: To clarify the genetic and infectious profiles of MS and neuromyelitis optica (NMO). Background The prevalence of multiple sclerosis (MS) is rapidly increasing and the age of onset is becoming younger in Japanese patients. Design/Methods: We analysed HLA-DRB1 and -DPB1 alleles, and IgG antibodies against helicobacter pylori, chlamydia pneumonia, varicella-zoster virus, and Epstein-Barr virus nuclear antigen in 145 MS patients, 122 NMO patients, and 367 healthy controls (HC). Results: As compared with HC, frequencies of DRB1*0405 and DPB1*0301 were significantly higher in MS patients, while those of DRB1*0901 and DPB1*0401 were significantly lower. By contrast, NMO patients showed significantly higher frequencies of DRB1*1602 and DPB1*0501 and a significantly lower frequency of DRB1*0901 compared with HC. MS patients with DRB1*0405 had a significantly earlier age of disease onset, and lower Kurtzke9s Expanded Disability Status Scale score, Progression Index and frequency of brain MRI lesions that met the Barkhof criteria than patients without this allele. The proportions and absolute numbers of DRB1*0405 showed a successive increase with advancing year of birth. Among individuals without DRB1*0405, the frequency of DRB1*1501 was significantly higher and that of DRB1*0901 was significantly lower in MS patients than in HC. DRB1*0405-negative MS patients showed a significantly higher frequency of anti-Epstein-Barr virus nuclear antigen antibodies as compared with HC, while anti-helicobacter pylori and anti-chlamydia antibodies were significantly higher only in anti-aquaporin-4 antibody-positive NMO patients. Conclusions: These findings suggest that the susceptibility genes vary according to the disease phenotype and that DRB1*0901 is a common protective allele, irrespective of the phenotype. DRB1*0405-positive MS patients showed an earlier age of disease onset and a relatively benign course with low brain lesion loads, while DRB1*0405-negative MS patients had similar trends to Caucasian MS patients in terms of high frequency of Epstein-Barr virus infection and presence of DRB1*1501. Disclosure: Dr. Yoshimura has nothing to disclose. Dr. Yonekawa has nothing to disclose. Dr. Isobe has nothing to disclose. Dr. Masaki has nothing to disclose. Dr. Satou has nothing to disclose. Dr. Matsushita has nothing to disclose. Dr. Kira has received personal compensation for activities with Bayer Pharmaceuticals Corporation and Biogen Idec as a speaker and/or consultant.Dr. Kira has received research support from Ministry of Health, Labour and Welfare, Japan, the Japan Science and Technology Agency, and the Ministry of Education, Science, Sports and Culture, Japan. Dr. Kira has received personal compensation in an editorial capacity for Multiple Sclerosis, The Open Neurology Journal, and Journal of the Neurological Sciences.