{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:06:38Z","timestamp":1790496398617,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T00:00:00Z","timestamp":1502841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 0.00001 odds ratio (OR), 16.88; 95% confidence intervals (CI): 11.27\u201325.28) 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\u20130.70); 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\u20131.81) 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.<\/jats:p>","DOI":"10.3390\/ijms18081775","type":"journal-article","created":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T10:43:51Z","timestamp":1502880231000},"page":"1775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese"],"prefix":"10.3390","volume":"18","author":[{"given":"Chin-Man","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33375, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 33375, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Jian","family":"Jan Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kuei-Shan, Taoyuan 33375, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kuei-Shan, Taoyuan 33375, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, Department of Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kuei-Shan, Taoyuan 33375, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1002\/1529-0131(200006)43:6<1356::AID-ANR20>3.0.CO;2-Y","article-title":"The familial form of spondylarthropathy: A clinical study of 115 multiplex families. 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