Journal
SEMINARS IN IMMUNOLOGY
Volume 18, Issue 4, Pages 214-223Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2006.03.009
Keywords
rheumatoid arthritis; genetics; phosphatase
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Funding
- NIAMS NIH HHS [R01-AR-44422, N01-AR2-2263] Funding Source: Medline
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The 620W allelic variant of the intracellular tyrosine phosphatase, PTPN22, is associated with a number of different autoimmune disorders, and this provides direct evidence for common mechanisms underlying many of these diseases. The associated allele appears to influence thresholds for T cell receptor signaling, and a variety of disease models involving both central and peripheral tolerance can be proposed. However, given the fact that PTPN22 is expressed in a variety of immunologically relevant cell types, the precise mechanisms for these associations remain unclear. In general, the PTPN22 620W allele appears to play a role in autoimmune disorders that have a prominent humoral component, suggesting that further investigation of PTPN22 activity in B cells will be useful. From a genetic perspective, the data highlights the genetic heterogeneity underlying autoimmunity in different ethnic groups. (C) 2006 Elsevier Ltd. All rights reserved.
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