<i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese
MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether <i>MICA</i> alleles are associated with AS susceptibility in Taiwanese. <i>MICA</i> alleles were determin...
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MDPI AG
2021-06-01
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| author | Chin-Man Wang Keng-Poo Tan Yeong-Jian Jan Wu Jing-Chi Lin Jian-Wen Zheng Alice L. Yu Jian-Ming Wu Ji-Yih Chen |
| author_facet | Chin-Man Wang Keng-Poo Tan Yeong-Jian Jan Wu Jing-Chi Lin Jian-Wen Zheng Alice L. Yu Jian-Ming Wu Ji-Yih Chen |
| author_sort | Chin-Man Wang |
| collection | DOAJ |
| description | MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether <i>MICA</i> alleles are associated with AS susceptibility in Taiwanese. <i>MICA</i> alleles were determined through haplotype analyses of major <i>MICA</i> coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of <i>MICA</i> alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major <i>MICA</i> alleles (<i>MICA</i>*<i>002</i>, <i>MICA</i>*<i>008</i>, <i>MICA</i>*<i>010</i> and <i>MICA</i>*<i>019</i>) in Taiwanese were used for biological analyses. We found that <i>MICA*019</i> is the only major <i>MICA</i> allele significantly associated with AS susceptibility (P<i><sub>FDR</sub></i> = 2.25 × 10<sup>−115</sup>; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the <i>MICA*019</i> allele is associated with syndesmophyte formation (P<i><sub>FDR</sub></i> = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and <i>HLA-B27</i> positivity (P<i><sub>FDR</sub></i> = 1.45 × 10<sup>−33</sup>; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, <i>MICA*019</i> homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing <i>MICA*019</i> produced the highest level of sMICA, as compared to other major <i>MICA</i> alleles. In summary, the <i>MICA</i>*<i>019</i> allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS. |
| first_indexed | 2024-03-10T10:21:55Z |
| format | Article |
| id | doaj.art-dc3ac59027664f07b83775008ad8a05a |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T10:21:55Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-dc3ac59027664f07b83775008ad8a05a2023-11-22T00:21:58ZengMDPI AGJournal of Personalized Medicine2075-44262021-06-0111656410.3390/jpm11060564<i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in TaiwaneseChin-Man Wang0Keng-Poo Tan1Yeong-Jian Jan Wu2Jing-Chi Lin3Jian-Wen Zheng4Alice L. Yu5Jian-Ming Wu6Ji-Yih Chen7Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 33375, TaiwanDepartment of Veterinary and Biomedical Sciences, Department of Medicine, University of Minnesota, Minneapolis, MN 55108, USADepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanMICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether <i>MICA</i> alleles are associated with AS susceptibility in Taiwanese. <i>MICA</i> alleles were determined through haplotype analyses of major <i>MICA</i> coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of <i>MICA</i> alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major <i>MICA</i> alleles (<i>MICA</i>*<i>002</i>, <i>MICA</i>*<i>008</i>, <i>MICA</i>*<i>010</i> and <i>MICA</i>*<i>019</i>) in Taiwanese were used for biological analyses. We found that <i>MICA*019</i> is the only major <i>MICA</i> allele significantly associated with AS susceptibility (P<i><sub>FDR</sub></i> = 2.25 × 10<sup>−115</sup>; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the <i>MICA*019</i> allele is associated with syndesmophyte formation (P<i><sub>FDR</sub></i> = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and <i>HLA-B27</i> positivity (P<i><sub>FDR</sub></i> = 1.45 × 10<sup>−33</sup>; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, <i>MICA*019</i> homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing <i>MICA*019</i> produced the highest level of sMICA, as compared to other major <i>MICA</i> alleles. In summary, the <i>MICA</i>*<i>019</i> allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.https://www.mdpi.com/2075-4426/11/6/564MICAASsoluble MICAHLA-B27syndesmophyte |
| spellingShingle | Chin-Man Wang Keng-Poo Tan Yeong-Jian Jan Wu Jing-Chi Lin Jian-Wen Zheng Alice L. Yu Jian-Ming Wu Ji-Yih Chen <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese Journal of Personalized Medicine MICA AS soluble MICA HLA-B27 syndesmophyte |
| title | <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese |
| title_full | <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese |
| title_fullStr | <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese |
| title_full_unstemmed | <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese |
| title_short | <i>MICA*019</i> Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese |
| title_sort | i mica 019 i allele and soluble mica as biomarkers for ankylosing spondylitis in taiwanese |
| topic | MICA AS soluble MICA HLA-B27 syndesmophyte |
| url | https://www.mdpi.com/2075-4426/11/6/564 |
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