B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

Abstract

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

Progress in treatment of neuromyelitis optica spectrum disorders (NMOSD): Novel insights into therapeutic possibilities in NMOSD

“…However, the therapeutic effects of these antibodies appeared only in AQP4‐IgG‐seropositive patients, not in AQP4‐IgG‐seronegative patients, indicating therapeutic response different in two groups 80 . Despite this, these antibodies have been demonstrated to be effective and promising therapeutic interventions in NMOSD 81 …”

“…80 Despite this, these antibodies have been demonstrated to be effective and promising therapeutic interventions in NMOSD. 81…”

Neuromyelitis Optica (NMO) — Study Review

“…A good option for patients with a poor response to steroids/PLEX/IA are intravenous immunoglobulins (IVIG). The treatment course is a dosage of 0.4 g/kg/d within 5 days [14].…”

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism

“…[5][6][7][8] B-cell depletion with the anti-CD20 monoclonal antibody rituximab is often empirically used for attack-prevention treatment. 9,10 Anti-CD19 and CD20 monoclonal antibodies are B-cell-specific markers, however, CD19 targets antibody-secreting plasmablasts, some plasma cells, and pre-B cells. 11,12 Importantly, CD19+ plasmablasts and plasma cells (PB/PC) are often elevated in patients with NMOSD, especially during an attack, suggesting that these B-cell subsets may play an integral role in attacks.…”

“…B‐cell depletion with the anti‐CD20 monoclonal antibody rituximab is often empirically used for attack‐prevention treatment 9,10 . Anti‐CD19 and CD20 monoclonal antibodies are B‐cell‐specific markers, however, CD19 targets antibody‐secreting plasmablasts, some plasma cells, and pre‐B cells 11,12 .…”