ESTABLISHED AND EMERGING IMMUNOLOGICAL DIAGNOSTIC APPROACHES FOR MYASTHENIA GRAVIS AND NEUROMYELITIS OPTICA SPECTRUM DISORDER

Abstract

Myasthenia Gravis (MG) and Neuromyelitis Optica spectrum disorder (NMOSD) are both antibody-mediated autoimmune neurological disorders whose diagnosis is based on clinical, imaging, and laboratory findings, and particularly on the detection of specific antibodies. Regarding their serological antibody status, most MG patients express antibodies against acetylcholine receptor (AChR) and fewer express antibodies against muscle specific kinase (MuSK) and the lipoprotein receptor-related protein-4 (LRP4). Similarly, most patients with NMOSD phenotype express antibodies against aquaporin-4 (AQP4), while fewer have antibodies against myelin oligodendrocyte glycoprotein (MOG). However, some “seronegative” patients pose diagnostic and therapeutic challenges, highlighting the importance of novel biomarkers and the parallel establishment of advanced diagnostic assays. In this review, we focus on presenting the established methodologies used to detect the related autoantibodies in each disease (such as immunoprecipitation and ELISA), as well as the role and principles of some of the latest techniques (such as cell-based immunofluorescence assays) in achieving an optimal patient diagnosis. Furthermore, we describe the current data on emerging immunological diagnostic approaches regarding potential biomarkers of tissue damage and complement activation, enriching the conventional serological testing with expanded autoantibody panels and markers. These advancements will enable clinicians to achieve a reliable diagnosis in previously “seronegative” patients and to effectively monitor patients to implement truly personalized therapeutic strategies.