Human leukocyte antigen c*12:02:02 and killer immunoglobulin-like receptor 2dl5 are distinctly associated with ankylosing spondylitis in the Taiwanese

Chin Man Wang, Sheng Hung Wang, Yeong Jian Wu, Jing Chi Lin, Jianming Wu, Ji Yih Chen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes. HLA-C alleles were functionally characterized using 3D structural modelling with peptide simulation. This study discovered that the HLA-C*12:02:02 allele (43.42% vs. 3.31%; p < 0.00001 odds ratio (OR), 16.88; 95% confidence intervals (CI): 11.27-25.28) confers a strong risk for Taiwanese AS development. The 3D modelling results identified four unique amino acid polymorphisms, Ala73, Trp156, Arg219 and Met304, that may affect the function of the HLA-C*12:02:02 allele. KIR2DL5 (p = 0.0047; pFDR = 0.0423) and the KIR Bx haplotype (p = 0.0000275) were protective against Taiwanese AS, while KIR 2DS4/1D (22 base pair truncated deletion; p = 0.0044; pFDR = 0.1998) appeared to be a risk factor for it. KIR2DL5 combined with the HLA-C1/C2 heterozygous genotype showed a protective effect (AS 5.97% vs. normal 11.66%; p = 0.002; pFDR = 0.0127, OR, 0.48 95% CI: 0.33-0.70); in contrast, KIR 2DS4/1D combined with the HLA-C1C1 homozygous genotype (AS 45.33% vs. normal 35.92%; p = 0.002; pFDR = 0.0127, OR, 1.48 95% CI: 1.21-1.81) represented a risk factor for AS development. Our data suggested that interactions between KIRs and their cognate HLA-C ligands may contribute to the pathogenesis of AS.

Original languageEnglish (US)
Article number1775
JournalInternational journal of molecular sciences
Volume18
Issue number8
DOIs
StatePublished - Aug 16 2017

Bibliographical note

Funding Information:
Acknowledgments: We greatly appreciate the Shin Chu Blood Donor Centre for the collection of blood samples and Su-Wei Chang for statistical analysis. This study was supported by funding from the Chang Gung Memorial Hospital (CMRPG3C0063 and CMRPG3F0052) and the Ministry of Science and Technology, Taiwan (105-2314-B-068-MY3).

Keywords

  • Ankylosing spondylitis
  • Human leukocyte antigen C (HLA-C)
  • Killer immunoglobulin-like receptor (KIR)
  • Natural killer cell

Fingerprint Dive into the research topics of 'Human leukocyte antigen c*12:02:02 and killer immunoglobulin-like receptor 2dl5 are distinctly associated with ankylosing spondylitis in the Taiwanese'. Together they form a unique fingerprint.

Cite this