Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1-encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti-double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell-dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses. Instead, T-dependent antibody responses were impaired in SH2D1A-deficient mice, reflecting defective germinal center formation. These findings demonstrate a specific role for the SLAM-SH2D1A system in the regulation of T-dependent humoral immune responses, implicating members of the CD150-SH2D1A family as targets in the pathogenesis and therapy of antibody-mediated autoimmune and allergic diseases.
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PMID:SH2D1A regulates T-dependent humoral autoimmunity. 1526 31

Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. SAP is expressed in T cells and natural killer (NK) cells and binds to the cytoplasmic domains of SLAM family receptors, resulting in the subsequent recruitment of Fyn. The SAP (SH2D1A) gene is located on the X chromosome and is responsible for X-linked lymphoproliferative disease, characterized by higher susceptibility to Epstein-Barr virus infection. The SAP-mediated signal is not only essential for the development of NKT cells, i.e. unconventional CD1d-restricted T cells with invariant Valpha14 T cell receptors, but also for the regulation of the function of NK cells and conventional T cells. The role of SAP-mediated signaling in the induction of autoimmune diseases has been analyzed using animal models such as lupus, hepatitis, and graft-versus-host disease and is considered important in their pathogenesis in humans. In this review we highlight the current findings on SAP-mediated signaling in hematopoietic cells and discuss its importance in autoimmune diseases and immunological disorders.
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PMID:Role of SLAM-associated protein in the pathogenesis of autoimmune diseases and immunological disorders. 2004 47

SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.
Lupus 2013 Apr
PMID:Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus. 2355 38