A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

•We systematically examined the three complement pathways during NMO remission.•Although the complement pattern is altered in the plasma, activation is unlikely.•Alterations suggest the influences of both the disease process and therapy.•Systemic complement studies might be of diagnostic value in NMO. Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61–82) vs. 65 (56–73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59–111) vs. 49 (3–92)%; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9–1.3) vs. 1.4 (1.2–1.5)g/L; p