X-linked lymphoproliferative syndrome (XLP) is caused by mutations in SH2D1A, and is associated with overwhelming infectious mononucleosis, aplastic anemia, hypogammaglobulinemia, and B-cell lymphomas.
Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development.
XLP caused by SAP deficiency is most often characterized by fulminant mononucleosis/EBV- associated hemophagocytic lymphohistiocytosis (HLH), lymphoma, and dysgammaglobulinemia.
The manifestations of XLP generally occur following Epstein-Barr virus (EBV) infection and include fulminant mononucleosis, hypogammaglobulinemia and lymphoma.
We suggest that T cells expressing CD244 and SLAM are responsible for the clinical features of IM but that the control of activation is maintained by parallel increased expression of SAP.
We identified mutations of the SH2D1A gene only in the majority of patients presenting with fatal mononucleosis or an XLP family history, but not in any of the other patients studied.
A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis based on the inability to control EBV.
Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma.
Further functional studies of the SH2D1A protein will probably provide new insights into the pathogenesis of severe infectious mononucleosis, malignant lymphomas and immunodeficiency in patients with XLP.