Evolution of Anti-B Cell Therapeutics in Autoimmune Neurological Diseases

Abstract

B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antigen-presenting cells facilitating antibody production but also as sensors, coordinators, and regulators of the immune response. In particular, B cells can regulate the T cell activation process through their participation in antigen presentation, production of proinflammatory cytokines (bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such an important interplay between B and T cells makes therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B cell therapies using monoclonal antibodies against B cell surface molecules have evolved into a rational approach for successfully treating autoimmune neurological disorders, even when T cells seem to be the main effector cells. The paper summarizes basic aspects of B cell biology, discusses the roles of B cells in neurological autoimmunities, and highlights how the currently available or under development anti-B cell therapeutics exert their action in the wide spectrum and immunologically diverse neurological disorders. The efficacy of the various anti-B cell therapies and practical issues on induction and maintenance therapy is specifically detailed for the treatment of patients with multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis and hyperexcitability CNS disorders, autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies. The success of anti-B cell therapies in inducing long-term remission in IgG4 neuroautoimmunities is also highlighted pointing out potential biomarkers for follow-up infusions.

Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy

“…Immunosuppressive agents - whether traditional, synthetic or biological - modulate or inhibit the expression of key target molecules for the immune response, and can therefore reduce the immunogenicity and efficacy of vaccines [ 5 ]. Anti-CD20 represent a class of drugs targeting B-cells used to treat IMID, including subjects who do not respond to other treatments [ 6 ] and patients treated with B-cell depleting agentsare at higher risk of hospitalization and a more severe course of COVID-19 [ 7 , 8 ]. Several real-world reports show proof of a reduced humoral response in patients exposed to immunotherapies after vaccination against COVID-19 [ [9] , [10] , [11] , [12] , [13] ].…”

Autoimmune Neurological Disorders with IgG4 Antibodies: a Distinct Disease Spectrum with Unique IgG4 Functions Responding to Anti-B Cell Therapies

“…(a) Inebilizumab, a monoclonal anti-CD19 antibody approved in neuromyelitis optica [73,74]. Of interest, an international, multi-center trial has already begun in 160 patients with IgG4-RD [2].…”

New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies

“…No evidence is available for new-generation anti-CD20 agents such as ocrelizumab, obinutuzumab, ublituximab, and veltuzumab in the treatment of MG, whereas new anti-CD19 treatments are being proposed [ 55 , 56 ]. A case of a patient with refractory AChR-MG responding to ofatumumab has been reported [ 57 ].…”

“…Anti-CD19 drugs could have some advantages over anti-CD20 agents, as the CD19 marker is expressed much earlier than CD20 in the B-cell maturation process and might act synergistically with anti-CD20 agents [ 55 ].…”