SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease

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SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in...

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Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP.

X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by infection with Epstein-Barr virus. Major disease manifestations include fatal acute infectious mononucleosis, B-cell lymphoma, and progressive dys-gammaglobulinemia. SAP/SH2D1A, the product of the gene mutated in XLP, is a small protein that comprises a single SH2 domain and a short tail of 26 amino acids...

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Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative disease gene Sap.

X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAP gene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG levels in Sap-deficient mice before and after viral infections, which are associated with impaired CD4+ T-helper function. In the present work, we find that...

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X-Linked Lymphoproliferative Disease

2B4 is a surface molecule involved in activation of the natural killer (NK) cell-mediated cytotoxicity. It binds a protein termed Src homology 2 domain-containing protein (SH2D1A) or signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which in turn has been proposed to function as a regulator of the 2B4-associated signal transduction pathway. In this study, we analyzed pat...

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Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP.

X-linked lymphoproliferative disease (XLP) is an immunodeficiency resulting from mutations in SH2D1A, which encodes signalling lymphocytic activation molecule (SLAM)-associated protein (SAP). In addition to SLAM, SAP associates with several other cell-surface receptors including 2B4 (CD244), Ly9 (CD229), CD84 and NTB-A. SAP contains a single src-homology-2 domain and acts as an intracellular ad...

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ژورنال

عنوان ژورنال: Blood

سال: 2013

ISSN: 0006-4971,1528-0020

DOI: 10.1182/blood-2012-07-445858