Moving beyond anti-aquaporin-4 antibodies: emerging biomarkers in the spectrum of neuromyelitis optica

Introduction: With the advent of targeted drugs, a correct identification of patients with neuromyelitis optica spectrum disorders (NMOSD) is fundamental. Moreover, to assess treatment efficacy, sensitive biomarkers for monitoring disease activity are needed. Areas covered: In this review, the authors provide an up-to-date guide to NMOSD biomarkers, starting from the pathogenetic mechanisms and moving to clinical findings, focusing on their diagnostic meaning, their possible application for disease monitoring and their correlation with clinical features. Expert opinion: Beside anti-AQP4-IgG, other emerging biomarkers for NMOSD have been proposed. Elements supporting antibody production, such as T Helper 17 and T Follicular Helper cells, plasmablasts, and their related cytokines, can be supportive criteria for NMOSD diagnosis since their levels are related to disease activity. Similarly, indices of granulocyte and complement activation, associated with markers of astrocyte damage, reflect disease status and correlate with clinical features. Among all cytokines, IL6 and IL17a represent the bridge between innate and acquired immunity and between cellular and humoral arms of the immune system, therefore being useful for both diagnosis and disease monitoring. Paraclinical tools, such as magnetic resonance imaging and optical coherence tomography, can provide useful diagnostic information, especially in double-seronegative patients.