Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

Abstract

B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or Bcell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.

Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies

“…Rituximab is a monoclonal antibody against CD20, a B-cell surface antigen present on pre-B cells and throughout the B-cell life cycle, but not on plasma cells. 52 – 54 Rituximab causes depletion of circulating B cells, prompting several trials.…”

“…Rituximab has an excellent safety profile, but infections from common bacteria or viral agents can occur. 36 , 52 – 54 Progressive multifocal leukoencephalopathy has been reported in some patients with B-cell malignancies receiving rituximab plus chemotherapy (R-CHOP, fludarabine). 36 , 52 , 54 , 71 Vigilance is recommended, especially in patients receiving concomitant immunosuppressants.…”

Rituximab treatment of myasthenia gravis: A systematic review

“…Rituximab produces a substantial reduction in circulating CD20 + B‐cells for up to 6 months after a cycle of infusions and is used as targeted therapy for the treatment of non‐Hodgkin B‐cell lymphoma, rheumatoid arthritis, Wegener granulomatosis, and microangiopathic vasculitis, indications for which it is approved by regulatory agencies in many countries. Recently, rituximab has been found to be effective in several other autoimmune diseases, including immune thrombocytopenia, autoimmune hemolytic anemia, type 1 diabetes mellitus, renal disorders, pemphigus, and several neurological diseases . There is evidence from case reports and series that rituximab treatment may be beneficial in MG, including in severe cases and in patients who are refractory to conventional immunomodulatory therapies.…”

“…Recently, rituximab has been found to be effective in several other autoimmune diseases, including immune thrombocytopenia, 17 autoimmune hemolytic anemia, 18 type 1 diabetes mellitus, 19 renal disorders, 20 pemphigus, 21 and several neurological diseases. 22 There is evidence from case reports and series that rituximab treatment may be beneficial in MG, including in severe cases and in patients who are refractory to conventional immunomodulatory therapies.…”

Neuro-Immunotherapies: A 30-year Retrospective of an Overwhelming Success and a Brighter Future

“…Bittner and Wiendl [4] discuss the ways of modifying the immune response to influence disease progression by targeting T-cell-associated transduction molecules, highlighting future molecular anti-T-cell therapies, especially in patients with MS. Alexopoulos et al [5] discuss the same principles for B cells, including B-cell trophic factors, emphasizing the role of B cells in neurological diseases and the unprecedented effect the anti-B-cell therapies are expected to play as neuroimmunotherapies in the immediate future. Lünemmn et al [6] summarize the evidence-based indications for the use of IVIg in neurology, including potential biomarkers of response to therapies, and future strategies on how to replace IVIg with recombinant products to enhance its antiinflammatory properties.…”