Antibodies against interferon-beta in neuromyelitis optica patients.

Abstract Neuromyelitis optica (NMO) is an antibody-mediated autoimmune inflammatory disease of the CNS. A poor response to treatment with recombinant interferon beta (IFN-s) in NMO patients has been suggested, although the precise mechanisms remain uncertain. We analyzed occurrence and clinical consequences of IFN-neutralizing antibodies (NAbs) in 15 IFN-s treated NMO-patients from a population-based retrospective case series cohort. NMO patients not treated with IFN-s acted as a reference group. IFN-s antibody determinations included binding antibodies (BAbs) measured by immunoassay and NAbs measured by a neutralization bioassay. Antibodies were determined 6–36 months after initiation of IFN-β therapy and NAbs additionally 5–10 years post-therapy. BAbs were detected in 14/15 NMO patients; 6/15 were NAbs-positive (3 at 5–10 years post-therapy) two of those anti-AQP4 antibody-positive; seven of the nine NAbs-negative patients were anti-AQP4 antibody-positive. Eleven patients (three NAbs-positive, eight NAbs-negative) developed cerebral lesions and 12 patients (four NAbs-positive, eight NAbs-negative) spinal cord lesions on magnetic resonance imaging as gadolinium positive lesions or T2-weighted lesions, at significantly higher frequencies than NMO reference group (p