RT Journal Article
T1 Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers.
A1 Egg, David
A1 Schwab, Charlotte
A1 Gabrysch, Annemarie
A1 Arkwright, Peter D
A1 Cheesman, Edmund
A1 Giulino-Roth, Lisa
A1 Neth, Olaf
A1 Snapper, Scott
A1 Okada, Satoshi
A1 Moutschen, Michel
A1 Delvenne, Philippe
A1 Pecher, Ann-Christin
A1 Wolff, Daniel
A1 Kim, Yae-Jean
A1 Seneviratne, Suranjith
A1 Kim, Kyoung-Mee
A1 Kang, Ji-Man
A1 Ojaimi, Samar
A1 McLean, Catriona
A1 Warnatz, Klaus
A1 Seidl, Maximilian
A1 Grimbacher, Bodo
K1 CMV
K1 CTLA4
K1 EBV
K1 cancer predisposition
K1 combined immunodeficiency
K1 malignancy
K1 primary immunodeficiency
AB 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.
YR 2018
FD 2018-09-10
LK http://hdl.handle.net/10668/12992
UL http://hdl.handle.net/10668/12992
LA en
DS RISalud
RD Apr 14, 2025