The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer
Open Access
- 19 June 2020
- Vol. 9 (6), 1498
- https://doi.org/10.3390/cells9061498
Abstract
Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.Funding Information
- European Regional Development Fund (NORTE-01-0145-FEDER-000003/000029)
This publication has 51 references indexed in Scilit:
- Transcriptional regulation of T helper type 2 differentiationImmunology, 2014
- Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levelsClinical and Experimental Immunology, 2012
- Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell DifferentiationPLOS ONE, 2011
- GATA-3 up-regulation in CD8+ T cells as a biomarker of immune dysfunction in systemic sclerosis, resulting in excessive interleukin-13 productionArthritis & Rheumatism, 2011
- Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programmeClinical and Experimental Immunology, 2011
- Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcerWorld Journal of Gastroenterology, 2010
- Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditionsBritish Journal of Haematology, 2009
- Autoimmunity in Common Variable ImmunodeficiencyJournal of Clinical Immunology, 2008
- Pathology of non‐infective gastritisHistopathology, 2006
- 143 Gastric Adenocarcinoma In a Boy with X-Linked AgammaglobulinemiaPediatric Research, 2004