CD20+ B Cell Depletion in Systemic Autoimmune Diseases: Common Mechanism of Inhibition or Disease-Specific Effect on Humoral Immunity?

Abstract

Autoimmunity remains a complex physiologic deviation, enabled and perpetuated by a variety of interplayers and pathways. Simplistic approaches, targeting either isolated end-effectors of more centrally placed interactors of these mechanisms, are continuously tried in an effort to comprehend and halt cascades with potential disabling and deleterious effects in the affected individuals. This review focuses on theoretical and clinically proved effects of rituximab-induced CD20+ B cell depletion on different systemic autoimmune diseases and extrapolates on pathogenetic mechanisms that may account for different interindividual or interdisease responses.

B cell Therapy to Treat an Axonal Neuropathy in Mixed Connective Tissue Disease

“…The evolving B cell lineage includes pro-B cells, pre-B cells, immature and transitional B cells, mature naive B cells, memory B cells, plasmablasts, and plasma cells. Plasmablasts are recently differentiated antibody-producing cells that are usually short-lived but can recirculate and settle in tissues such as the mucosa or the bone marrow, where they can differentiate into fully mature antibodyproducing plasma cells [1,2]. The B cellspecific antigen CD20 is expressed during B cell development, starting at the pre-B cell level (not found on stem cells or early pre-B cells), and persists through B cell differentiation, but is lost during terminal differentiation to plasma cells [1].…”

“…Terminally differentiated antibody producing cells (long-lived plasma cells) may not express CD20 on their surface [1]. As such, scheduled retreatment of RA with rituximab q 16 to 24 weeks would not wipe out all repopulated B cells [7] (see Figure 1).…”

Produção de novos anticorpos Anti-CD20 na forma de FvFc em células de mamíferos

“…Porém essa resposta é bem maior quando o rituximabe é usado para o tratamento de doenças autoimunes e leva a uma tolerização à terapia (de Lorenzo-Pinto et al, 2013;España et al, 2013;Mayes et al, 2011;Shuptrine et al, 2012;Stathis and Ghielmini, 2012).Com o intuito de minimizar os efeitos adversos dos anticorpos anti-rituximabe e aumentar a atividade efetora da terapia a busca por anticorpos molecularmente engenheirados é feita por vários grupos de pesquisa. (Alduaij and Illidge, 2011;de Lorenzo-Pinto et al, 2013;Fernández et al, 2015;Holliger and Hudson, 2005;Maloney, 2012;Pateinakis and Pyrpasopoulou, 2014;van Oers and Kersten, 2011).…”

“…É um anticorpo monoclonal específico para antígeno CD20, o qual é uma fosfoproteína de membrana que regula a condutância de cálcio, sendo expresso nos linfócitos B normais, nos linfoma não-Hodgkin derivados de células B e em 93% e nas células da leucemia linfócítica crônica até em 99% (Alduaij and Illidge, 2011;Binder et al, 2006;Fernández et al, 2015;Herter et al, 2013;Pateinakis and Pyrpasopoulou, 2014 (Du et al, 2007;Fernández et al, 2015).…”

“…Muito menos se expressa nas células plasmáticas e em seus derivados oncogênicos ou em componentes de linfócitos T (Binder et al, 2006;Fernández et al, 2015;Pateinakis and Pyrpasopoulou, 2014). Uma das vantagens do alvo antigênico é não ser interno para conectar-se ao anticorpo monoclonal e por sua expressão ser estável.…”