Background Killer cell immunoglobulin like receptors (KIR) expressed on NK and T cell subsets interact with HLA ligands to influence the reactivity of these cells. The KIR/HLA genotype of an individual can affect immune responses to infection and susceptibility to autoimmunity based on the number/type of genes present (1-3).
Objectives The aim of this study was to evaluate KIR/HLA-C genotypes and haplotypes in rheumatoid arthritis patients and healthy controls.
Methods One hundred and fifty one rheumatoid arthritis (RA) patients and 100 healthy controls (HC) were DNA typed for 15 KIR genes and HLA-C group 1 and 2 alleles by PCR-SSP. KIR gene content in each group was determined by direct counting and broad haplotypes AA and Bx were assigned. The Bx haplotype was defined by the presence of inhibiting KIR 2DL2, 2DL5 and/or activating KIR 2DS1, 2DS2, 2DS3, 2DS5 or 3DS1. In the AA haplotype all these genes are absent.
Results Comparison of individual KIR gene content between the RA group and controls did not show any significant differences. The availability of HLA-C1 and C2 ligands for inhibitory KIR was also similar between the RA and HC groups, C1/C1 (50%), C2/C2 (10%), C1/C2 (40%). Analysis of KIR genotypes and haplotype assignation revealed that the Bx haplotype which contains more than one activating KIR was significantly more frequent in the RA group compared to controls (76% vs. 60 %; P = 0.01).
Conclusions Prevalence of the Bx haplotype in this RA population and subsequent availability of more activating KIR on NK and T cells could promote inflammatory responses in this disease.
Kakoo SI et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C infection. Science 2004; 305:872–4.
Nelson GW et al. Heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in Psoriatic arthritis. J Immunol 2004;173:4273–6
Hollenbach JA et al. Susceptibility to Crohn’s disease is mediated by KIR2DL2/KIR2DL3 heterozygosity and the HLA-C ligand. Immunogenetics 2009; 61:633–71.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.