Wang Chin-Man, Tan Keng-Poo, Wu Yeong-Jian Jan, Zheng Jian-Wen, Wu Jianming, Chen Ji-Yih
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, Taiwan.
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan.
Int J Mol Sci. 2024 Mar 6;25(5):3036. doi: 10.3390/ijms25053036.
As the principal ligand for NKG2D, MICA elicits the recruitment of subsets of T cells and NK cells in innate immunity. MICA gene variants greatly impact the functionality and expression of MICA in humans. The current study evaluated whether polymorphisms distinctively influence the pathogenesis of psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in Taiwanese subjects. The distributions of alleles and levels of serum soluble NKG2D were compared between healthy controls and patients with PSO, RA, and SLE, respectively. The binding capacities and cell surface densities of MICA alleles were assessed by utilizing stable cell lines expressing four prominent Taiwanese alleles. Our data revealed that *010 was significantly associated with risks for PSO and RA (P = 1.93 × 10 and 0.00112, respectively), while *045 was significantly associated with predisposition to SLE (P = 0.0002). On the other hand, *002 was associated with protection against RA development (P = 4.16 × 10), while *009 was associated with a low risk for PSO (P = 0.0058). *002 exhibited the highest binding affinity for NKG2D compared to the other alleles. Serum concentrations of soluble MICA were significantly elevated in SLE patients compared to healthy controls ( = 0.01). The lack of cell surface expression of the *010 was caused by its entrapment in the endoplasmic reticulum. As a prevalent risk factor for PSO and RA, *010 is deficient in cell surface expression and is unable to interact with NKG2D. Our study suggests that alleles distinctively contribute to the pathogenesis of PSO, RA, and SLE in Taiwanese people.
作为NKG2D的主要配体，MICA在先天免疫中引发T细胞和NK细胞亚群的募集。MICA基因变异极大地影响了MICA在人类中的功能和表达。本研究评估了多态性是否对台湾受试者中银屑病（PSO）、类风湿性关节炎（RA）和系统性红斑狼疮（SLE）的发病机制有独特影响。分别比较了健康对照与PSO、RA和SLE患者之间的等位基因分布及血清可溶性NKG2D水平。通过利用表达四种主要台湾等位基因的稳定细胞系评估了MICA等位基因的结合能力和细胞表面密度。我们的数据显示，010与PSO和RA的风险显著相关（P分别为1.93×10和0.00112），而045与SLE的易感性显著相关（P = 0.0002）。另一方面，002与预防RA发生相关（P = 4.16×10），而009与PSO的低风险相关（P = 0.0058）。与其他等位基因相比，*002对NKG2D表现出最高的结合亲和力。与健康对照相比，SLE患者血清可溶性MICA浓度显著升高（P = 0.01）。*010缺乏细胞表面表达是由于其被困在内质网中。作为PSO和RA的常见风险因素，*010缺乏细胞表面表达且无法与NKG2D相互作用。我们的研究表明，等位基因对台湾人群中PSO、RA和SLE的发病机制有独特贡献。
