X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

Booth, Claire; Gilmour, Kimberly C.; Veys, Paul; Gennery, Andrew R.; Slatter, Mary; Chapel, Helen; Heath, Paul T; Steward, Colin G.; Smith, Owen; O'Meara, Anna; Kerrigan, Hilary; Mahlaoui, Nizar; Cavazzana, Marina; Fischer, Alain; Moshous, Despina; Blanche, Stéphane; Schmid, Jana Pachlopnik; Latour, Sylvain; Basile, Geneviève de Saint; Albert, Michael H.; Notheis, Gundula; Rieber, Nikolaus; Strahm, Brigitte; Ritterbusch, Henrike; Lankester, Arjan C.; Hartwig, Nico G.; Meyts, Isabelle; Plebani, Alessandro; Soresina, Annarosa; Finocchi, Andrea; Pignata, Claudio; Cirillo, Emilia; Bonanomi, Sonia; Peters, Christina; Kałwak, Krzysztof; Pašić, Srdjan; Sedláček, Petr; Jazbec, Janez; Kanegane, Hirokazu; Nichols, Kim E.; Hanson, I. Celine; Kapoor, Neena; Haddad, Élie; Cowan, Morton J.; Choo, Sharon; Smart, Joanne; Arkwright, Peter D.; Gaspar, H. Bobby

doi:10.1182/blood-2010-06-284935

Cited by 275 publications

(301 citation statements)

References 42 publications

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“…The cohort investigated here included only a limited number of hyper-IgM syndrome patients, and none carried any of the five reported APDS mutations. Autoimmune phenomena, enteropathies and blood dyscrasias feature strongly in lipopolysaccharideresponsive and beige-like anchor protein (LRBA) deficiency, another condition with a profile of combined immunodeficiency and autoimmunity [23,24], while massive EBV-driven B cell lymphoproliferation and possibly EBVassociated lymphoma is characteristic of deficiencies of interleukin 2-inducible T cell kinase (ITK) [25][26][27], CD27 [28,29] and X-linked lymphoproliferative disease caused by mutations in SH2D1A [30].…”

Section: Discussionmentioning

confidence: 99%

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

Elgizouli

Lowe

Speckmann

et al. 2015

Clinical and Experimental Immunology

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SummaryThe gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase d (PI3Kd), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kd syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.

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Section: Discussionmentioning

confidence: 99%

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

Elgizouli

Lowe

Speckmann

et al. 2015

Clinical and Experimental Immunology

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“…The resultant cytokine storm triggers haemophagocytic lymphohistiocytosis (HLH), leading in most cases to fatal bone marrow failure. Other boys with the same trait present with hypogamma-globulinaemia or B cell lymphoma, conditions that are not linked to (and may precede) EBV infection [66][67][68]. The XLP gene SH2D1A encodes a small adapter protein, SAP, that is expressed in T, NK and i-NKT cells and is involved in the signalling of cell-cell interactions mediated by members of the SLAM family of surface receptors [69] Interestingly, XLP patients have normal numbers of NK and T cells but lack i-NKT cells, fuelling speculation that i-NKT cells may play a role in controlling EBV.…”

Section: The Special Case Of Xlp and Its Relative Xiapmentioning

confidence: 99%

Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory

Rickinson

Long

Palendira

et al. 2014

Trends in Immunology

110

104

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Epstein-Barr virus (EBV), a human herpesvirus with potent B cell growth transforming ability, induces multiple cellular immune responses in the infected host. How these host responses work together to prevent virus pathogenicity, and how immune imbalance predisposes to disease, remain poorly understood. Here, we describe three ongoing lines of enquiry that are shedding new light on these issues. These focus on: (i) patients with infectious mononucleosis or its fatal equivalent, X-linked lymphoproliferative disease; (ii) EBV infection in a range of new, genetically defined, primary immune deficiency states; and (iii) experimental infection in two complementary animal models, the rhesus macaque and the human haemopoietic stem cell reconstituted mouse.

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“…As with SCID, results of transplant are better if patients are transplanted whilst younger, without end organ damage. For those with XLP, survival from transplant is significantly better for patients who do not experience haemophagocytic lymphohistiocytosis [58]. In a similar fashion, for patients with chronic granulomatous disease, outcome is better in those that have not had significant fungal infection or inflammatory sequalae [24].…”

Section: Other Primary Immunodeficienciesmentioning

confidence: 54%

Stem Cell Transplantation for Primary Immunodeficiency

Slatter¹,

Gennery²

2012

Immunodeficiency

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X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

Cited by 275 publications

References 42 publications

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency

Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory

Stem Cell Transplantation for Primary Immunodeficiency

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