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Erschienen in: Journal of Clinical Immunology 1/2016

01.01.2016 | Astute Clinician Report

A Patient with CTLA-4 Haploinsufficiency Presenting Gastric Cancer

verfasst von: Seiichi Hayakawa, Satoshi Okada, Miyuki Tsumura, Sonoko Sakata, Yoshitaka Ueno, Kohsuke Imai, Tomohiro Morio, Osamu Ohara, Kazuaki Chayama, Masao Kobayashi

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2016

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Abstract

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-4high 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.
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Metadaten
Titel
A Patient with CTLA-4 Haploinsufficiency Presenting Gastric Cancer
verfasst von
Seiichi Hayakawa
Satoshi Okada
Miyuki Tsumura
Sonoko Sakata
Yoshitaka Ueno
Kohsuke Imai
Tomohiro Morio
Osamu Ohara
Kazuaki Chayama
Masao Kobayashi
Publikationsdatum
01.01.2016
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 1/2016
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-015-0221-x

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