Egg, David and Schwab, Charlotte and Gabrysch, Annemarie and Arkwright, Peter D. and Cheesman, Edmund and Giulino-Roth, Lisa and Neth, Olaf and Snapper, Scott and Okada, Satoshi and Moutschen, Michel and Delvenne, Philippe and Pecher, Ann-Christin and Wolff, Daniel and Kim, Yae-Jean and Seneviratne, Suranjith and Kim, Kyoung-Mee and Kang, Ji-Man and Ojaimi, Samar and McLean, Catriona and Warnatz, Klaus and Seidl, Maximilian and Grimbacher, Bodo (2018) Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers. FRONTIERS IN IMMUNOLOGY, 9: 2012. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNE DYSREGULATION; GASTRIC-CANCER; LRBA; DEFICIENCY; IPILIMUMAB; NIVOLUMAB; MELANOMA; DISEASES; CTLA4; combined immunodeficiency; primary immunodeficiency; malignancy; cancer predisposition; EBV; CMV |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Dec 2019 08:39 |
| Last Modified: | 13 Dec 2019 08:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13870 |
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