Prognostic implications of aquaporin-4 antibody status in neuromyelitis optica patients

Abstract

Neuromyelitis optica (NMO) is an inflammatory/demyelinating disorder predominantly affecting the optic nerves and spinal cord. Recent findings showed an underlying humoral abnormality in NMO, characterized by a serum antibody against aquaporin-4 (Aqp-4-Ab). In this study, we evaluated the Aqp-4-Ab status among Turkish patients with NMO to determine the clinical and prognostic relevance. Serum samples from 35 consecutive patients with NMO followed at a single center and diagnosed according to the 2006 revised criteria, were evaluated for Aqp-4-Ab. All samples were obtained during a relapse prior to any immunosuppressive treatment. Aqp-4-Ab was positive in 21/35 (60%) patients. Among these cases, 11 had an EDSS of 6.0 or more, whereas only two patients in the seronegative group had such severe disability (p < 0.05). Overall, seropositive cases had a mean EDSS score of 5.1 ± 2.2 compared with 3.5 ± 1.7 in seronegative cases (p < 0.01). There were trends towards female predominance in seropositive cases and a monophasic course predominance in seronegative cases. Disease duration, age at onset, number of attacks and time to definite NMO did not differ between groups. Our findings in this single-center cohort suggest that the presence of Aqp-4-Ab might have a prognostic significance indicating a more severe disease course.

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders

“…The reasons for sex differences in the prevalence of autoreactive autoantibodies are not fully understood, but they might be of importance as NMO/SD possibly takes a more severe course in seropositive patients. 4,25,26 Sex differences in predisposition and course of auto immune diseases are, first and foremost, assumed to be based on differences in immunocompetence and immune reactivity. Hormonal factors, for example, differences in circulating sex hormones or changes in hormone receptor expression are supposed to be involved in sex differences in autoimmune diseases.…”

Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

“…In 60-80% of cases, NMO is associated with antibodies to aquaporin-4 (AQP4ab), the most abundant water channel in the CNS, and its presence is related to a relapsing and often worse disease course [26][27][28] .…”

Influenza-associated Monophasic Neuromyelitis Optica

“…All patients with monophasic NMO were seronegative for NMO-IgG and recovered well, in the similar course to the present patient (4). Other studies have also described low rates of NMO-IgG seropositivity in pediatric or adult patients with monophasic NMO (10,12). NMOIgG-seropositive patients had frequent recurrence and severe disabilities compared to seronegative patients (3,(10)(11)(12).…”

“…Other studies have also described low rates of NMO-IgG seropositivity in pediatric or adult patients with monophasic NMO (10,12). NMOIgG-seropositive patients had frequent recurrence and severe disabilities compared to seronegative patients (3,(10)(11)(12). Therefore, the pathogenesis seems to differ between NMOIgG-seropositive and NMO-IgG-seronegative p-NMO.…”

“…Aside from the clinical course of NMO patients and different sensitivities of various NMO-IgG detection assays, the frequency of NMO-IgG seropositivity has been suggested to depend on ethnicity (9,(12)(13)(14). Moreover, there is the possibility that NMO-IgG-seronegative monophasic p-NMO may be a parainfectious disorder (4).…”