Primary immunodeficiencies and the control of Epstein–Barr virus infection

Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1

“…RASGRP1 deficiency should now be considered among the growing number of primary immunodeficiencies associated with susceptibility to EBV and EBV-driven malignancy, particularly in patients with susceptibility to viral infections [9]. Further studies are necessary to dissect why intact RASGRP1 signaling is particularly important for control of EBV.…”

Atypical manifestations of Epstein-Barr virus: red alert for primary immunodeficiencies

“…In both diseases, patients could present severe infectious mononucleosis; and acute disease could result in a cytokine storm that causes macrophage activation and hemophagocytic lymphohistiocytosis (HLH). 2 The diseases in this group showed an increased susceptibility not only to EBV, but also to other herpes virus family and, in some cases, to HPV. 6 Group 2 contains PIDs caused by mutations in genes CD27 (CD27 deficiency, AR), MAGT1 (XMEN syndrome, X-linked), ITK (ITK deficiency, AR), CORO1A (coronin-1A deficiency, AR), FCGR3 (CD16 deficiency, AR), and MCM4 (MCM4 deficiency, AR).…”

“…4,5 The advance in the genetic approaches in the last years has increased the pace at which causative genes for PIDs are being discovered. 2 Group 1 includes the X-linked lymphoproliferative diseases type 1, caused by SH2D1A gene mutations, and type 2, associated with XIAP gene mutations. 2 Group 1 includes the X-linked lymphoproliferative diseases type 1, caused by SH2D1A gene mutations, and type 2, associated with XIAP gene mutations.…”

“…5 Recently, Palendira and Rickson, in a educational and simple method, divided PID patients into groups to explain the susceptibility to EBV infections: (1) PIDs that are selectively susceptible to EBV; (2) PIDs with broader virus susceptibility, but frequent EBV disease; (3) PIDs generally susceptible to viral and nonviral infections; and (4) PIDs with an inherent susceptibility to lymphoma. 2,4 In another review, authors added three different PIDs to this group, including mutations in the genes PRF1 (perforin deficiency, autosomal recessive (AR)), STXBP2 (munc18-2 deficiency, AR), and UNC13D (munc13-4 deficiency, AR), which are also associated with HLH and the development of chronic and severe EBV disease. In both diseases, patients could present severe infectious mononucleosis; and acute disease could result in a cytokine storm that causes macrophage activation and hemophagocytic lymphohistiocytosis (HLH).…”

“…6 Group 2 contains PIDs caused by mutations in genes CD27 (CD27 deficiency, AR), MAGT1 (XMEN syndrome, X-linked), ITK (ITK deficiency, AR), CORO1A (coronin-1A deficiency, AR), FCGR3 (CD16 deficiency, AR), and MCM4 (MCM4 deficiency, AR). 2,4,6 The PIDs in group 4 present different degrees of immune system deficiency, which are also associated with increased cancer incidence and the involvement of EBV in some of these tumors, especially lymphomas. 4 Group 3 has complex PIDs with different predispositions to several microorganisms, including EBV infections.…”