| Title: |
Increased risk for malignancies in 131 affected CTLA4 mutation carriers |
| Authors: |
Egg, D; Schwab, C; Gabrysch, A; Arkwright, PD; Cheesman, E; Giulino-Roth, L; Neth, O; Snapper, S; Okada, S; Moutschen, M; Delvenne, P; Pecher, AC; Wolff, D; Kim, YJ; Seneviratne, S; Kim, KM; Kang, JM; Ojaimi, S; McLean, C; Warnatz, K; Seidl, M; Grimbacher, B |
| Publisher Information: |
FRONTIERS MEDIA SA |
| Publication Year: |
2018 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://hdl.handle.net/11343/271257 |
| Availability: |
https://hdl.handle.net/11343/271257 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.846B09B4 |
| Database: |
BASE |