Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

• MeSH
• akvaporin 4 genetika   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoglobulin G MeSH
• lidé MeSH
• neuromyelitis optica * farmakoterapie   genetika   MeSH
• receptory IgG genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akvaporin 4 MeSH
• FCGR3A protein, human MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• imunoglobulin G MeSH
• inebilizumab MeSH Prohlížeč
• receptory IgG MeSH

Cumulative evidence along several lines indicates that B cells play an important role in the pathological course of multiple sclerosis (MS), neuromyelitisoptica spectrum disorders (NMOSD) and related CNS diseases. This has prompted extensive research in exploring the utility of targeting B cells to contain disease activity in these disorders. In this review, we first recapitulate the development of B cells from their origin in the bone marrow to their migration to the periphery, including the expression of therapy-relevant surface immunoglobulin isotypes. Not only the ability of B cells to produce cytokines and immunoglobulins seems to be essential in driving neuroinflammation, but also their regulatory functions strongly impact pathobiology. We then critically assess studies of B cell depleting therapies, including CD20 and CD19 targeting monoclonal antibodies, as well as the new class of B cell modulating substances, Bruton´s tyrosinekinase (BTK) inhibitors, in MS, NMOSD and MOGAD.

• Klíčová slova
• B cell depletion, autoimmune disease of the central nervous system, multiple sclerosis (MS), myelin oligodendrocyte glycoprotein associated autoimmune disease (MOGAD), neuromyelitisoptica spectrum disorders (NMOSD),
• MeSH
• autoimunitní nemoci * farmakoterapie   MeSH
• autoprotilátky MeSH
• B-lymfocyty MeSH
• centrální nervový systém MeSH
• lidé MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• autoprotilátky MeSH