Killer immunoglobulin-like receptor (KIR) repertoire analysis in a Caucasian Spanish population with inflammatory bowel diseases

Immunological molecules are implicated in inflammatory disorders, including IBD [CD and UC]. A further group of genetically variable proteins involved in immune function are killer cell immunoglobulin-like receptors (KIRs). These are expressed by NK cells and certain T lymphocytes where they regulate specificity and function by interaction with HLA Class I molecules. KIRs may either be inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations of activating KIRs with certain autoimmune and inflammatory diseases have been demonstrated. However, there are several conflicting articles of KIR association with IBD and their relationships seem to be unclear. The aim of this study was to determine the relationship between KIR repertoire and the IBD pathologies in a Spanish population. KIR variability analysis was performed using PCR-SSOP. We found an increased frequency in inhibitory KIR2DL5 in UC and IBD patient groups respect to Controls (P = 0.028 and P = 0.01, respectively, but Pc > 0.05) and in the same manner an increased frequency in 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 the eventual imbalance between activating and inhibitory KIR may make sense, at least in part, to the differential pathogenesis of these IBDs and could also suggest a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.