%0 Journal Article
%A Egg, David
%A Schwab, Charlotte
%A Gabrysch, Annemarie
%A Arkwright, Peter D
%A Cheesman, Edmund
%A Giulino-Roth, Lisa
%A Neth, Olaf
%A Snapper, Scott
%A Okada, Satoshi
%A Moutschen, Michel
%A Delvenne, Philippe
%A Pecher, Ann-Christin
%A Wolff, Daniel
%A Kim, Yae-Jean
%A Seneviratne, Suranjith
%A Kim, Kyoung-Mee
%A Kang, Ji-Man
%A Ojaimi, Samar
%A McLean, Catriona
%A Warnatz, Klaus
%A Seidl, Maximilian
%A Grimbacher, Bodo
%T Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers.
%D 2018
%U http://hdl.handle.net/10668/12992
%X Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown. Methods: Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184 CTLA4 mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled. Results: Among the 184 CTLA4 mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected CTLA4 mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated. Conclusion: Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected CTLA4 mutation carriers.
%K CMV
%K CTLA4
%K EBV
%K cancer predisposition
%K combined immunodeficiency
%K malignancy
%K primary immunodeficiency
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