期刊
IMMUNOLOGY LETTERS
卷 259, 期 -, 页码 37-45出版社
ELSEVIER
DOI: 10.1016/j.imlet.2023.05.005
关键词
Autoimmunity; Autoreactivity; B cells; Autoantibody; Antigen-specific; Tolerance
类别
Autoimmune diseases are characterized by a breakdown of immunological tolerance to self, resulting in an abnormal immune response to self-antigens. The pathogenesis is driven by a complex interaction between autoreactive B and T cells. B cell targeting therapies, such as Rituximab, have shown efficacy in reducing symptoms of autoimmune diseases, but can also lead to infections. Therefore, antigen-specific approaches to target autoreactive cells are being investigated.
Autoimmune diseases are heterogeneous pathologies characterized by a breakdown of immunological tolerance to self, resulting in a chronic and aberrant immune response to self-antigens. The scope and extent of affected tissues can vary greatly per autoimmune disease and can involve multiple organs and tissue types. The patho-genesis of most autoimmune diseases remains unknown but it is widely accepted that a complex interplay be-tween (autoreactive) B and T cells in the context of breached immunological tolerance drives autoimmune pathology. The importance of B cells in autoimmune disease is exemplified by the successful use of B cell tar-geting therapies in the clinic. For example, Rituximab, a depleting anti-CD20 antibody, has shown favorable results in reducing the signs and symptoms of multiple autoimmune diseases, including Rheumatoid Arthritis, Anti-Neutrophil Cytoplasmic Antibody associated vasculitis and Multiple Sclerosis. However, Rituximab depletes the entire B cell repertoire, leaving patients susceptible to (latent) infections. Therefore, multiple ways to target autoreactive cells in an antigen-specific manner are currently under investigation. In this review, we will lay out the current state of antigen-specific B cell inhibiting or depleting therapies in the context of autoimmune diseases.
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