Estudio de HLA de clase I y KIR en artritis reumatoide

Résumé

BACKGROUND Rheumatoid Arthritis (AR) is an immune mediated chronic disease of unknown cause. Genetic susceptibility has been located in type I and mainly type II mayor human histocompatibility complex (HLA). KIRs (Killer immunoglobulin like receptors) recognize among other ligands type I HLA molecules and are capable for activating natural killer cells inducing an innate immune response; NK cells can also promote a persistent adaptive immune response, typical in RA. Inheritance of KIR receptors is complex and two different haplotypes, A and B, are defined. Haplotype A is well conserved and codes for fewer and more inhibitory receptors while haplotype B codifies a more variable set of KIRs with more activating receptors. Everyone has two sets of KIR genes composed by an independent centromeric and telomeric portion. MATERIALS AND METHODS Case control study of allelic frequency of class I HLA, KIR genes and KIR haplotypes in 151 RA patients and 150 controls. DNA was extracted from peripheral blood samples and genotyping performed using a PCR-SSP technique. Research restricted to case-control differences and associations between these alleles and clinical manifestations, disease activity, quality of life, laboratory findings or treatment profile among RA patients. RESULTS A significative association was found between RA and haplotype B, KIR2DS3 and centromeric haplotype B01 compared to control population. RA centromeric haplotype B01 patients associated to homozygosity for Bw6 compared to controls and less rheumatoid nodules, positivity for rheumatoid factor or double positivity (RF and ACPA), lower mean titles of RF, ACPA, C3 and C4 among RA patients. In KIR2DS3 positive RA patients RF title was also significantly lower. HLA-A*03 associated with positive RF or ACPA in RA patients. CONCLUSIONS Study results of class I HLA and KIR interaction in RA suggest a more prominent influence of KIR genes and KIR haplotype in our population, especially in seronegative patients with no rheumatoid nodules. It is of interest to explore the influence of group Bw6 and other potential ligands for KIR receptors in RA pathogenesis.