MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese.
MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese.
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DOI：
10.3390/jpm11060564
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发表时间：
2021-06-16
影响因子：
--
通讯作者：
Chen JY
中科院分区：
文献类型：
--
作者：
Wang CM;Tan KP;Jan Wu YJ;Lin JC;Zheng JW;Yu AL;Wu JM;Chen JY
云母（主要组织相容性复合体I类链相关基因A）与免疫细胞上的NKG 2D相互作用，以调节宿主免疫应答。我们的目的是确定云母等位基因是否与台湾人AS易感性相关。通过对台湾895名AS患者和896名正常健康对照者的主要云母编码SNP（cSNP）数据进行单倍型分析，确定云母等位基因。比较云母等位基因在AS患者和正常健康对照之间的分布，以及按临床特征分层的AS患者之间的分布。采用ELISA法检测AS患者和健康对照者血清中可溶性云母（sMICA）水平。使用在台湾表达四种主要云母等位基因（云母 *002、云母 *008、云母 *010和云母 *019）的稳定细胞系进行生物学分析。我们发现云母 *019是台湾人中唯一与AS易感性显著相关的主要云母等位基因（PFDR = 2.25 × 10−115; OR，14.90; 95%CI，11.83-18.77）。此外，在AS患者中，云母 *019等位基因与联合韧带赘生物形成（PFDR = 0.0017; OR，1.69; 95%CI，1.29-2.22）和HLA-B27阳性（PFDR = 1.45 × 10−33; OR，28.79; 95%CI，16.83-49.26）相关。与健康对照组相比，AS患者血清sMICA水平显著升高。此外，与具有其他基因型的供体相比，云母 *019纯合子受试者产生最高水平的sMICA。此外，体外实验显示，与其他主要云母等位基因相比，表达云母 *019的细胞产生最高水平的sMICA。总之，云母 *019等位基因，产生最高水平的sMICA，是一个重要的危险因素，为AS和关节韧带形成在台湾。我们的数据表明，高水平的sMICA是AS的生物标志物。
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 MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA 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 MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; 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, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 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.
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影响因子：
11.2
作者：
Ashiru O;Boutet P;Fernández-Messina L;Agüera-González S;Skepper JN;Valés-Gómez M;Reyburn HT
通讯作者：
Reyburn HT
影响因子：
3.7
作者：
Muñoz-Saá, I.;Cambra, A.;Julià, M. R.
通讯作者：
Julià, M. R.
影响因子：
7.3
作者：
Isernhagen A;Malzahn D;Bickeböller H;Dressel R
通讯作者：
Dressel R
影响因子：
4.4
作者：
Dalbeth, N;Gundle, R;Callan, MFC
通讯作者：
Callan, MFC
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T