Polymorphisms of KIRs Gene and HLA-C Alleles in Patients with Ankylosing Spondylitis: Possible Association with Susceptibility to the Disease
- 186 Downloads
An emerging body of evidence is accumulating to suggest that killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands contribute to the pathogenesis of diverse kinds of autoimmune diseases. However, the functional effects of their polymorphism remain largely unknown to date. Thus, the present study was undertaken to determine the association of the polymorphisms KIRs gene and HLA-C alleles with the susceptibility to ankylosing spondylitis (AS) by means of polymerase chain reaction/sequence-specific primers for genotyping KIRs from genomic DNA of 119 patients with AS together with 128 healthy donors as a control group.
Results and Discussion
We found that the frequencies of KIR3DS1 and KIR2DL5 were statistically significantly higher in the patient group than those in the control group (P = 0.016 and P = 0.003, respectively). Meanwhile, the percentage of patients, who were carrying two or more of the activating KIRs, was higher than that of control group. With respect to HLA-C alleles, individuals with AS showed an increased frequency of HLA-Cw02. If HLA-C was divided into group 1 or group 2 based on whether there was an asparagine or lysine present at position 80 of the alpha-chain, HLA-C group 2 was more common in subjects with AS compared to control subjects. The genotype 2DS1+/HLA-C lys80+ was more common in subjects with AS. Moreover, the CD69 expression, a NK activation marker, remarkably increased in patient with AS.
In conclusions, this study suggests that KIR3DS1 may severe as AS susceptive genes to trigger continuous injury of arthrosis. The imbalance of activating and inhibitory KIR as well as HLA-C group 1 and group 2 may be the key factor, which influences the pathogenesis of AS. Moreover, KIR2DS1 might associate with the susceptibility of AS by influencing NK cell activity once group 2 HLA-C ligands are present.
KeywordsImmunoglublin-like receptors human leukocyte antigen spondylitis ankylosing genotyping
This study was supported by Chinese National Natural Science Foundation grants 30371304 and Shandong Provincial Natural Science Foundation grants yz2006c72 to Dr. Y.R. Zhao.
- 12.Moretta A, Vitale M, Bottino C, Orengo AM, Morelli L, Augugliaro R, Barbaresi M, Ciccone E, Moretta L. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells: anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med. 1993;178:597–604.PubMedCrossRefGoogle Scholar
- 13.Martin MP, Nelson G, Lee JH, Pellett F, Gao X, Wade J, Wilson MJ, Trowsdale J, Gladman D, Carrington M. Cutting edge: susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles. J Immunol. 2002;169:2818–22.PubMedGoogle Scholar
- 18.Karlsen TH, Boberg KM, Olsson M, Sun JY, Senitzer D, Bergquist A, Schrumpf E, Thorsby E, Lie BA. Particular genetic variants of ligands for natural killer cell receptors may contribute to the HLA associated risk of primary sclerosing cholangitis. J Hepatol. 2007;46:899–906.PubMedCrossRefGoogle Scholar
- 23.Vilches C, Gardiner CM, Parham P. Gene structure and promoter variation of expressed and nonexpressed variants of the KIR2DL5 gene. J Immunology 2000;165:6416–21.Google Scholar
- 27.Lopez-Larrea C, Blanco-Gelaz MA, Torre-Alonso JC, Bruges Armas J, Suarez-Alvarez B, Pruneda L, Couto AR, Gonzalez S, Lopez-Vazquez A, Martinez-Borra J. Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations. Arthritis Res Ther. 2006;8:R101.PubMedCrossRefGoogle Scholar
- 28.Arno R, van der Slik B, Koeleman PC, Verduijn W, Bruining GJ, Roep BO, Giphart MJ. KIR in type 1 diabetes disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects. Diabetes. 2003;52:2638–3642.Google Scholar