Table 1. Human PIDs manifesting as severe EBV-induced disease
Mutated geneClinical featuresInfectionsOutcomesReferences
SH2D1A (XLP-1); n > 100age of onset: 0.5–40 yr; EBV viremia (65%); severe FIM/HLH (∼50–60%); hypogammaglobulinemia (40–50%); B lymphoma (Burkitt’s/NHL; often EBV) ∼25%EBV∼30–75% mortality (depends on study in relation to discovery of SH2D1A gene mutation in 1998); successfully treated with HSCTCoffey et al., 1998; Nichols et al., 1998; Sayos et al., 1998; Sumegi et al., 2000; Booth et al., 2011; Pachlopnik Schmid et al., 2011; Tangye, 2014
XIAP (XLP-2); n > 100age of onset: 0.5–40 yr; EBV viremia (50–60%); severe FIM/HLH (∼50–90%); splenomegaly/hepatitis (50–80%); inflammatory bowel disease (10–25%), cytopenias; transient hypogammaglobulinemia (10%)EBV; CMV, HHV6∼40–80% mortality; poor outcomes after HSCTRigaud et al., 2006; Filipovich et al., 2010; Marsh et al., 2010; Pachlopnik Schmid et al., 2011; Speckmann et al., 2013; Aguilar and Latour, 2015
ITK; n = 13age of onset: 3–13 yr; EBV viremia (100%); EBV-induced lymphoproliferation (∼70%); EBV+ B cell lymphoma (mostly Hodgkin’s; 1 NHL; 1 Burkitt’s lymphoma; ∼70%); CD4+ T cell lymphopenia (∼65%); splenomegaly (∼60%); progressive hypogammaglobulinemia (>50%); autoimmunity (infrequent; ∼20%)EBV; CMV, VZV∼60–65% mortality; 2/3 patients successfully treated with HSCTHuck et al., 2009; Linka et al., 2012; Mansouri et al., 2012; Ghosh et al., 2014; Bienemann et al., 2015; Cipe et al., 2015; Çağdaş et al., 2017
MAGT1; (X-MEN) n = 11age of onset: 3–45 yr; chronic EBV viremia (100%); EBV-induced lymphoproliferation (not HLH); EBV+ B lymphoma (Burkitt’s/Hodgkin’s/ DLBCL; 70%); CD4+ T cell lymphopenia (∼50%); splenomegaly; progressive hypogammaglobulinemia (>50%)EBV; VZV, HSV, CMV, KSHV, molluscum contagiosum∼30% mortality; poor outcomes after HSCTLi et al., 2011; Chaigne-Delalande et al., 2013; Dhalla et al., 2015; Patiroglu et al., 2015; Brigida et al., 2016
CD27; n = 17age of onset: 1–22 yr; EBV viremia (∼90%); severe HLH (∼25%); EBV-induced lymphoproliferation (∼50%); EBV+ B lymphoma (Hodgkin’s, DLBCL; ∼50%); hypogammaglobulinemia (∼70%)EBV; VZV, CMV (<15%); recurrent bacterial/viral infections∼30% mortality; 3/3 patients successfully treated with HSCTvan Montfrans et al., 2012; Salzer et al., 2013; Alkhairy et al., 2015
CD70; n = 5age of onset: 1–5 yr; EBV viremia (100%); EBV-lymphoproliferation (80%); EBV+ B lymphoma (Hodgkin’s; 80%); hypogammaglobulinemia (60–80%)EBV; VZV, CMV (50%); recurrent bacterial/viral infectionsall patients currently aliveAbolhassani et al., 2017; Izawa et al., 2017
NFKB1; n = 2age of onset: 14–15 yr; EBV viremia; lymphoproliferation, hepatosplenomegaly; hypogammaglobulinemiaEBV; recurrent viral/ bacterial/fungal infectionsalive and awaiting HSCTBoztug et al., 2016; Schipp et al., 2016
RASGRP1; n = 1age of onset: 12 yr; EBV+ B lymphoma; CD4+ T cell lymphopeniaEBV; recurrent bacterial/viral infectionssuccessful HSCTSalzer et al., 2016

Abbreviations used: DLBCL, diffuse large B cell lymphoma; FIM, fulminant IM; HHV6, human herpesvirus 6; KSHV, Kaposi’s sarcoma herpes virus; NHL, non-Hodgkin’s lymphoma.