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Killer immunoglobulin‐like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease
Authors:Ruth López‐Hernández  Jose A Campillo  Isabel Legaz  Mariano Valdés  Hortensia Salama  Francisco Boix  AM Hernández‐Martínez  Jorge Eguia  G González‐Martínez  Maria R Moya‐Quiles  Alfredo Minguela  Ana García‐Alonso  Fernando Carballo  Manuel Muro
Institution:1. Immunology and Digestive Medicine Service, University Clinical Hospital Virgen de la Arrixaca‐IMIB, Murcia 30120 Spain;2. Digestive Medicine Service, University Clinical Hospital Virgen de la Arrixaca‐IMIB, Murcia 30120 Spain;3. Department of Third Generation Sequencing. Anthony Nolan Institute, 77B Fleet Road Hampstead, London NW3 2QU, UK;4. Biomedical Investigation Center in Net of Hepatic and Digestive Diseases, Immunology Service, University Clinical Hospital Virgen de la Arrixaca‐IMIB, Murcia, Spain
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.
Keywords:Crohn disease  inflammatory bowel disease  killer cell immunoglobulin‐like receptor polymorphism  ulcerative colitis
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