Identification of a specific autoantigen in opticospinal form of multiple sclerosis based on the HLA-DPB1 binding motif

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Multiple sclerosis (MS) is currently hypothesized to be mediated by autoreactive T cells against myelin antigens. In Japanese, MS frequently and selectively affects the optic nerve and spinal cord. We have previously reported that the opticospinal form of MS (OS-MS) has been shown to be distinct from the conventional form of MS (C-MS) clinically, immunologically and immunogenetically. Recently, oligodendrocytes have been demonstrated to have plural origins, showing marked differences in distribution depending on their origin. We assumed that the specific autoantigens which exist in the optic nerve and spinal cord may be associated with development of OS-MS lesions.To identify the autoantigens in OS-MS, we made use of an immunoscreening of a human spinal cord cDNA expression library with serum samples obtained from patients with OS-MS. cDNA expression library was prepared from human spinal cord and 5 X 10^5 to 10 X 10^5 phage plaques were immunoscreened with sera obtained from eight OS- … More MS patients. Eleven positive immunoreactive clones were identified by their reactivity to the sera, and their sequences were analyzed. Comparisons of the sequences showed that these clones represented cDNAs from 5 distinct genes (HSP105, Rabaptin-5, NSD1, KIAA1640, KIAA0640). We produced GST-Rabaptin-5 fusion protein and HSP105 protein and evaluated the titer of IgG anti-Rabaptin-5 and anti-HSP105 autoantibody in sera and CSF, using ELISA. We found IgG anti-Rabaptin-5 reactivities were not significantly elevated, however IgG anti-HSP105 reactivities in MS patients was significantly higher than those in normal controls (p = 0.0193). Anti-HSP105 reactivities were found in 3 % (2/66) of normal controls, while 14.5 % (10/69) of patients with MS were positive for anti-HSP105 antibodies. The difference in prevalence of autoantibodies was not statistically significant between OS-MS and C-MS. The HSP105 α-reactive T cell lines derived from CD4^+CD45RO^+ T cells were established from 3 of 9 MS patients but not normal controls. Our findings indicate HSP105 to be a novel candidate autoantigen in MS. In future, we are going to analyze the other candidate autoantigens (NSD1, KIAA1640, KIAA0610). Less