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Review

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

, &
Pages 601-618 | Received 04 Mar 2020, Accepted 30 Apr 2020, Published online: 29 May 2020
 

ABSTRACT

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.

Article highlights

  • Both B cell- and T cell-related immunity are likely to exert a central role in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD);

  • T Helper 17 and T Follicular Helper produce IL17a and IL6 cytokines, which promote granulocyte and B-cell activation, are higher in NMOSD than multiple sclerosis (MS) patients, and increase during clinical relapses;

  • Complement activity is enhanced in NMOSD and the combined dosage of C1 inhibitor, C5, and terminal complex may be a useful tool for the differential diagnosis of NMOSD;

  • The combined measurement of markers related to astrocyte damage (glial fibrillary acidic protein [GFAP], S100 calcium-binding protein B [S100B]), demyelination (myelin basic protein), and neuronal injury (neurofilaments) can help in NMOSD diagnosis;

  • GFAP and S100B levels correlate with the extent of structural damage and with clinical disability;

  • Neurophysiologic tests can contribute to rule out demyelinating disorders like MS, as the presence of severe delay of evoked potentials and asymptomatic neurophysiologic alterations are rare in NMOSD patients;

  • The presence of subclinical retinal vasculopathy in NMOSD patients is an emerging concept. Retinal vascular density and ganglion-cell inner plexiform layers can be altered in the absence of optic neuritis and might be helpful in disease diagnosis and monitoring;

  • Magnetic resonance imaging-based algorithms allow a correct identification of NMOSD patients with a high accuracy and may be a useful tool in AQP4-seronegative patients;

  • At the state of the art, no biomarkers anticipating NMOSD relapses are available.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.

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