Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody

Because Asian patients with opticospinal multiple sclerosis (OSMS) frequently have anti-aquaporin-4 (AQP4) antibody, complement-mediated disruption of astrocyte foot processes is proposed but not yet proven. We aimed to clarify whether complement consumption occurs at relapse in anti-AQP4 antibody-positive patients.

We analyzed serum CH50, C3, C4, and C-reactive protein (CRP) levels and their relation to clinical phases in 118 MS patients with or without anti-AQP4 antibody. Serum CH50 levels were higher in 24 patients with anti-AQP4 antibody than in 39 OSMS and 54 conventional form of MS (CMS) patients without anti-AQP4 antibody at relapse (Pcorr<0.05) but not in remission. The frequency of hypercomplementemia at relapse was also higher in anti-AQP4 antibody-positive patients than in anti-AQP4 antibody-negative CMS patients (70.4% vs 29.0%, Pcorr<0.05). C3 and C4 levels did not differ significantly among the three groups at relapse. In patients with anti-AQP4 antibody, the coexistence of hypercomplementemia and high CRP values was more common at relapse than in the remission phase (36.0% vs 10.5%, P<0.05). In patients with extensive central nervous system lesions, hypercomplementemia was significantly more common in anti-AQP4 antibody-positive patients than anti-AQP4 antibody-negative ones (88.9% vs 16.7%, P<0.01). We consider that hypercomplementemia in anti-AQP4 antibody-positive patients may reflect a systemic inflammatory reaction at relapse.