Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 36, Issue 1, Pages 28-32Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-015-0221-x
Keywords
CTLA-4; FOXP3; Autosomal dominant immune dysregulation syndrome; Gastric cancer; Regulatory Tcells
Categories
Funding
- Japan Society for the Promotion of Science [25293231, 26670501, 25713039, 25670477]
- Japanese Ministry of Health, Labour and Welfare [201324051A, 201324062A]
- Grants-in-Aid for Scientific Research [25670477, 15K21189, 25293231, 26670501, 25713039] Funding Source: KAKEN
Ask authors/readers for more resources
Cytotoxic T-lymphocyte-antigen 4 (CTLA-4) is an essential negative regulator expressed on regulatory T cells (Tregs) and activated T cells. Germline heterozygous mutations in CTLA4 lead to haploinsufficiency of CTLA-4, resulting in the development of an autosomal dominant immune dysregulation syndrome with incomplete penetrance. We report here a Japanese patient with this disorder who has a novel heterozygous single nucleotide insertion, 76_77insT (p. L28SfsX40), in the CTLA4 gene. Peripheral blood mononuclear cells from the patient showed decreased frequency of CTLA-4(high) cells in CD4(+)FOXP3(+) cells following CD3/CD28 stimulation. The patient experienced hypogammaglobulinemia, recurrent pneumonia, esophageal candidiasis, cytomegalovirus-positive chronic gastritis, chronic and severe diarrhea, and type 1 diabetes mellitus. Moreover, the patient developed multifocal gastric cancer, histologically poorly and well-differentiated adenocarcinomas, associated with chronic atrophic gastritis and intestinal metaplasia. Previously, 23 symptomatic cases with heterozygous CTLA4 mutations have been reported. Including the case presented here, 3 of the 24 cases (12.5 %) developed gastric cancer. Notably, 2 of 3 patients presented similarly multifocal adenocarcinomas associated with atrophic gastritis and intestinal metaplasia. Predisposition to gastric cancer has been also reported in CVID patients. These clinical observations suggest that gastric cancer is a disease commonly associated with autosomal dominant immune dysregulation syndrome due to CTLA4 mutation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available