Abstract
Spleen tyrosine kinase (Syk) is a member of the Src family of non-receptor tyrosine kinases, which associates directly with surface receptors, including B-cell receptor and Fcγ receptor, and is involved in a variety of signal transduction pathways. Rheumatoid arthritis (RA) and systemic lupus erythematosus are autoimmune diseases in which autoantibodies, immune complexes, and autoreactive T cells account for the expression of tissue inflammation and damage. Syk inhibitors efficiently suppress RA in patients albeit in the expression of unwanted side effects, including gastrointestinal effects, hypertension, and neutropenia. Syk inhibitors also inhibit clinical manifestations in lupus-prone mice. Here, we review the evidence that supports the use of Syk inhibitors to treat rheumatic and other autoimmune diseases.
Highlights
Targeting Spleen tyrosine kinase (Syk) in Autoimmune Rheumatic DiseasesReviewed by: Mohey Eldin El Shikh, Queen Mary University of London, UK Benedikt Fritzsching, University of Heidelberg, Germany
Spleen tyrosine kinase (Syk) is a cytoplasmic protein-tyrosine kinase and a member of the Src family of non-receptor tyrosine kinases [1]
The expression of Syk is increased in the skin lesion of lupus MRL/lpr mice [48], and the Syk inhibitor R788 completely abrogates skin inflammation induced by lupus serum (Deng, unpublished data)
Summary
Reviewed by: Mohey Eldin El Shikh, Queen Mary University of London, UK Benedikt Fritzsching, University of Heidelberg, Germany. Spleen tyrosine kinase (Syk) is a member of the Src family of non-receptor tyrosine kinases, which associates directly with surface receptors, including B-cell receptor and Fcγ receptor, and is involved in a variety of signal transduction pathways. Rheumatoid arthritis (RA) and systemic lupus erythematosus are autoimmune diseases in which autoantibodies, immune complexes, and autoreactive T cells account for the expression of tissue inflammation and damage. Syk inhibitors efficiently suppress RA in patients albeit in the expression of unwanted side effects, including gastrointestinal effects, hypertension, and neutropenia. Syk inhibitors inhibit clinical manifestations in lupus-prone mice. We review the evidence that supports the use of Syk inhibitors to treat rheumatic and other autoimmune diseases
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