Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP)

Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients

“…Thereafter, in many cases the disease progresses to a fatal aplastic phase, first involving macrophage activation (thought to be initiated by NK and T cell-derived cytokines), then hemophagocytosis, and eventually bone marrow failure. 28,33,34 At this point the clinical symptoms of XLP resemble those of another very rare complication of primary EBV infection, the EBV-associated hemophagocytic syndrome (EBV-AHS). 35,36 Very interestingly, it now appears that EBV-AHS stems from the aberrant infection and virus-driven expansion of NK-and/or T-cell subsets in the blood, leading to a cytokine storm and ensuing macrophage activation and hemophagocytosis 37 ; survivors of the acute infection thereafter harbor EBV in circulating NK or T cells.…”

Impaired Epstein-Barr virus–specific CD8+ T-cell function in X-linked lymphoproliferative disease is restricted to SLAM family–positive B-cell targets

“…2 Other phenotypes seen in XLP include the development of malignancies, predominantly of B-cell origin such as Burkitt lymphoma, or hypogammaglobulinaemia, which may predate or be unrelated to EBV exposure. 3 The genetic defect in XLP patients has been mapped to mutations in the signaling lymphocytic activation molecule (SLAM; CD150) associated protein (SAP). This small SH2 domain containing protein binds to immunoreceptor tyrosine-based switch motifs present in the cytoplasmic tails of SLAM receptor family membrane proteins, which include CD150, CD244, natural killer (NK)-, T-, and B-cell antigen (NTBA), CD84, CD229, and CD2-like receptor-activating cytotoxic cell (CRACC; reviewed in Ma et al 4 ).…”

Increased proliferation of CD8+ T cells in SAP‐deficient mice is associated with impaired activation‐induced cell death

“…X-linked lymphoproliferative syndrome (XLP), an abnormal immune response to EBV infection characterized by fatal infectious mononucleosis, dys-gammaglobulinemia and B cell lymphoma, is caused by mutations in the SH2D1A gene, which encodes signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) [1][2][3][4]. The adaptor SAP binds with high affinity to tyrosine motifs in the cytoplasmic domain of SLAM family immune receptors, including SLAM (CD150), CD244, CD229, SLAMF6, SLAMF7 and CD84, suggesting that SAP functions are important in modulating signals initiated by the SLAM family receptors [5][6][7][8].…”