Molecular immunogenetic approach to the pathogenesis of multiple sclerosis

In Japanese, there is no association of susceptibility to multiple sclerosis with any HLA class II alleles as a whole group. However, when we clinically classified MS patients into those having opticospinal form MS which presented selective involvement of the optic nerve and spinal cord and those with conventional form MS showing multiple involvement of the central nervous system including cerebrum, cerebellum and brainstem, the former showed a significant association with HLA-DPB1*0501 allele while the latter had an association with HLA-DRB1* 1501 allele. The patients with opticospinal form MS showed a marked Th1/Tc1 shift both in the relapse phase and in the remission phase, as determined by an intracellular IFN-γ/IL-4 ratio in peripheral blood CD4⁺ T cells and CD 8⁺ T cells. These findings suggest that opticospinal form MS is also an organ-specific autoimmune disease associated with a distinct HLA allele. By using SEREX method and brain proteomics approach, we have thus searched for any relevant autoantigens in the central nervous system in Japanese patients with MS. Heat shock proteins and neural proteins are found to be possible new candidate autoantigens in Japanese patients with MS.