Chapter 22 - The X-Linked Lymphoproliferative Syndromes

Abstract

The X-linked lymphoproliferative (XLP) syndromes are rare primary immunodeficiencies caused by germline mutations in SH2D1A and XIAP, which encode the proteins SAP and XIAP, respectively. Deficiencies in the XLP-associated proteins result in a shared susceptibility to develop hemophagocytic lymphohistiocytosis (HLH) and dysgammaglobulinemia. SAP-deficient patients develop HLH following primary Epstein-Barr virus (EBV) infection, while XIAP-deficient patients develop HLH in response to a variety of infectious triggers. In addition to HLH, SAP deficiency is associated with the onset of non-malignant or malignant lymphoproliferative disorders and, less commonly, vasculitis and aplastic anemia. XIAP deficiency is not associated with these latter manifestations, but instead some patients develop enterocolitis. The SAP and XIAP proteins do not share structural or functional similarities, and, given the differences in disease phenotypes, SAP and XIAP deficiency appear to represent two genetically and pathologically distinct disorders of the immune system.