Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma
| Autor: | Fang Liao, Sung-Hsin Kuo, Hsu Yc, Li-Tzong Chen, Yang Yc, Cathy S.J. Fann, Lin Jt, Ming-Shiang Wu, Ping-Ning Hsu, Chung-Wu Lin, Ann-Lii Cheng, Chen Jp |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Polymorphism Single Nucleotide Helicobacter Infections Pathogenesis Interleukin 22 Stomach Neoplasms Cell Line Tumor medicine Gastric mucosa Genetic predisposition Humans Genetic Predisposition to Disease biology Helicobacter pylori business.industry Interleukins Interleukin Hematology Lymphoma B-Cell Marginal Zone medicine.disease biology.organism_classification Lymphoma Neoplasm Proteins Gene Expression Regulation Neoplastic Lymphatic system medicine.anatomical_structure Oncology Immunology Original Article Female business |
| Zdroj: | Blood Cancer Journal |
| ISSN: | 2044-5385 |
| Popis: | Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication. |
| Databáze: | OpenAIRE |
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