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西班牙白种人炎症性肠病队列中的杀伤性免疫球蛋白样受体库分析

Killer immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease.

作者信息

López-Hernández Ruth, Campillo Jose A, Legaz Isabel, Valdés Mariano, Salama Hortensia, Boix Francisco, Hernández-Martínez A M, Eguia Jorge, González-Martínez G, Moya-Quiles Maria R, Minguela Alfredo, García-Alonso Ana, Carballo Fernando, Muro Manuel

机构信息

Immunology and Digestive Medicine Service, University Clinical Hospital Virgen de la Arrixaca-IMIB, Murcia 30120 Spain.

Digestive Medicine Service, University Clinical Hospital Virgen de la Arrixaca-IMIB, Murcia 30120 Spain.

出版信息

Microbiol Immunol. 2016 Nov;60(11):787-792. doi: 10.1111/1348-0421.12447.

Abstract

Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.

摘要

免疫分子与包括炎症性肠病(IBD;克罗恩病[CD]和溃疡性结肠炎[UC])在内的炎症性疾病有关。杀伤细胞免疫球蛋白样受体(KIR)也是参与免疫功能的遗传可变蛋白。它们由自然杀伤细胞(NK细胞)和某些T淋巴细胞表达,通过与I类人类白细胞抗原(HLA)分子相互作用来调节特异性和功能,可能具有抑制或激活作用,并且在等位基因和单倍型基因含量方面都是多态性的。已有报道激活型KIR与某些自身免疫性疾病和炎症性疾病之间存在遗传关联;然而,KIR与IBD之间可能存在的关联仍不明确。本研究的目的是确定西班牙人群中KIR基因谱与IBD病理之间的关系。使用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)分析KIR的变异性。发现抑制性KIR2DL5在UC患者组和IBD患者组中比在健康对照组中更常见(分别为P = 0.028和P = 0.01),激活型KIR2DS1也是如此(P = 0.02,校正P>0.05,UC与对照组相比;P = 0.001,校正P = 0.01,IBD与对照组相比;P = 0.01,校正P>0.05,对照组与CR相比),KIR2DS5(P = 0.0028,校正P = 0.04,对照组与UC相比;P = 0.0

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