Liao F, Hsu Y-C, Kuo S-H, Yang Y-C, Chen J-P, Hsu P-N, Lin C-W, Chen L-T, Cheng A-L, Fann C S J, Lin J-T, Wu M-S
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
1] Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan [2] Center for Database Research, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
Blood Cancer J. 2014 Oct 10;4(10):eXX. doi: 10.1038/bcj.2014.70.
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, P<0.006). 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.
慢性幽门螺杆菌刺激引发的免疫反应决定了胃黏膜相关淋巴组织（MALT）淋巴瘤的发病机制。我们旨在探究这种淋巴瘤的遗传易感性及其临床意义。对总共68例患者和140名无关对照进行了基因分型，检测了编码细胞因子、趋化因子及相关受体的基因中的84个单核苷酸多态性，这些基因在T细胞介导的胃肠道免疫中发挥重要作用。白细胞介素-22（IL-22）中的五种基因型，即rs1179246位点的CC型、rs2227485位点的CC型、rs4913428位点的AA型、rs1026788位点的AA型以及rs7314777位点的TT型，与疾病易感性相关。前四种基因型位于同一个连锁不平衡区域（r(2)=0.99），其患病风险大约高出三倍。体外实验表明，将外周血单个核细胞或CD4(+) T细胞与幽门螺杆菌共同培养可刺激白细胞介素-22（IL-22）的分泌，并且IL-22可诱导胃上皮细胞中抗菌蛋白RegIIIα和脂质运载蛋白-2的表达。此外，胃组织表达IL-22的患者对幽门螺杆菌根除治疗更可能产生反应（14/22对比4/19，P<0.006）。我们得出结论，胃MALT淋巴瘤的易感性受IL-22基因多态性的影响，IL-22的产物参与针对幽门螺杆菌的黏膜免疫，并与肿瘤对幽门螺杆菌根除治疗的反应相关。
