Aquaporin 4 antibody positive central nervous system autoimmunity and multiple sclerosis are characterized by a distinct profile of antibodies to herpes viruses

Viral infections are implicated in the onset and promotion of autoimmunity in genetically predisposed individuals. In this study, immune response patterns to herpes viruses were compared in aquaporin 4 (AQP4) antibody positive central nervous system (CNS) autoimmunity and multiple sclerosis (MS). Serum samples of patients with AQP4 antibody positive CNS autoimmunity (n=52), relapsing-remitting MS (n=55) and controls including non-autoimmune neurological disorders and healthy individuals (n=56) were tested for IgG antibodies to herpes viruses 1-6 (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6) using commercial ELISA kits. AQP4 antibody positive CNS autoimmunity cases most frequently had IgG responses to four viruses (38.5%), while presence of antibodies to three herpes viruses was most common in MS and controls (41.8% and 35.7%, respectively). Compared to MS, AQP4 positive cases had a significantly higher CMV seropositivity rate (P=0.003) and a lower prevalence of EBV antibodies (P=0.01). The analysis of immunoreactivity of samples above the diagnostic threshold revealed that in AQP4 positive CNS autoimmunity the IgG response to EBV (P<0.001) and VZV (P<0.01) was lower than in MS, whereas immununoreactivity to HSV-1 was higher than in controls (P<0.01). The distinct pattern of seroprevalence and immunoreactivity against herpes viruses in AQP4 positive CNS autoimmunity and MS provide further insights to the pathogenetical heterogeneity. Whether these findings reflect an epi-phenomenon of autoimmune disorders or indicate a disease-specific deregulated virus-host interaction needs to be examined in further studies.