Multiple sclerosis and aquaporin-4 autoimmune syndrome

Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. We found that the anti-AQP4 antibody positivity rate was higher in patients with OSMS (32.7%), idiopathic recur rent myelitis (23.5%), or recurrent optic neuritis (26.9%) as compared to that seen for conventional MS (CMS) patients (8.0%) and others (0%). The anti-AQP4 antibody titer was significantly higher in patients with the SS-A/B antibodies than in those without, but was not significantly correlated with either the EDSS score or the disease phase. Patients with a high anti-AQP4 antibody titer (≥ 512) showed significantly higher frequencies of extensive brain lesions and other autoantibodies/autoimmune diseases when compared to the anti-AQP4 antibody- seronegative OSMS patients that had longitudinally extensive spinal cord lesions. However, paradoxically, the former group showed significantly lower frequencies of acute transverse myelitis and severe motor disability than the latter, despite the fact that the optic nerve impairment was equally severe between the two. Extensive brain lesions in patients with high antibody titers showed a vasogenic edema pattern on diffusion-weighted magnetic resonance images. Anti- AQP4 antibody-seronegative OSMS patients showed a marked Thl shift in peripheral blood while such a shift was not observed in anti-AQP4 antibody- seropositive patients. These findings suggest that high titers of anti-AQP4 antibody are produced as a result of heightened humoral autoimmunity and the presence of the HLA-DPB1*0501 allele in Japanese. Additionally, they also contribute to extensive lesion development through the disturbed resolution of the vasogenic edema.