Taotao Li, Na Gao, Juan Du, Limin Zhao, Shiyu Yang, Yaxin Zhang, Junming Zhu, Haiou Hu, Zhiyu Qiao, Wei Cui, Lili Pan
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引用次数: 0
Abstract
Coronary artery involvement (CAI) is a special but not rare manifestation of Takayasu arteritis (TAK). Granzyme B (GzmB) is a multifunctional protease associated with the immune system and coronary artery disease. However, its role in patients with TAK and CAI remains unclear. This study investigates the role of GzmB+ cell subsets in TAK. The study included 105 TAK patients and 58 healthy controls. The percentages of different GzmB+ cells in blood samples were analyzed by flow cytometry. We found that age, age at onset, BMI, disease duration month, hypertension, and hyperlipidemia were significantly different between TAK patients with and without CAI (P=0.000, P=0.038, P=0.003, P=0.031, P=0.039, P=0.000). The proportions of CD3+CD8+cells (P=0.001) and CD3+CD4+cells (P=0.000) in GzmB+ cells were significantly increased, while the proportion of CD3-CD56+cells (P=0.001) in GzmB+ cells was decreased in TAK patients. The proportions of three types of GzmB+ subsets in lymphocytes (CD3+CD4+GzmB+, CD3+CD8+GzmB+, CD3+CD56+ GzmB+) were higher in TAK patients with CAI compared to those without CAI (P=0.021, P=0.007, P=0.007). The increased proportion of CD3+CD8+GzmB+cells/lymphocytes was an independent risk factor for coronary involvement in TAK (OR=4.990 [1.766-14.098], P=0.002). Additionally, patients with a high CD3+CD8+GzmB+cells/lymphocytes ratio had a higher MACE rate than those with a low ratio in TAK (P=0.019). Our results indicate that CD8 cell-derived Gzm B may be a predictor for CAI and MACE in TAK patients. Targeting CD3+CD8+GzmB+ lymphocytes or using GzmB inhibitors could be a potential therapeutic approach for the treatment of CAI in TAK.
冠状动脉受累(CAI)是高安动脉炎(TAK)的一种特殊表现,但并不罕见。颗粒酶 B(GzmB)是一种与免疫系统和冠状动脉疾病相关的多功能蛋白酶。然而,它在 TAK 和 CAI 患者中的作用仍不清楚。本研究调查了GzmB+细胞亚群在TAK中的作用。研究对象包括105名TAK患者和58名健康对照者。通过流式细胞术分析了血液样本中不同GzmB+细胞的百分比。我们发现,年龄、发病年龄、体重指数、病程月数、高血压和高脂血症在有 CAI 和无 CAI 的 TAK 患者之间存在显著差异(P=0.000、P=0.038、P=0.003、P=0.031、P=0.039、P=0.000)。在TAK患者中,GzmB+细胞中CD3+CD8+细胞(P=0.001)和CD3+CD4+细胞(P=0.000)的比例显著增加,而GzmB+细胞中CD3-CD56+细胞(P=0.001)的比例降低。与无CAI的TAK患者相比,有CAI的TAK患者淋巴细胞中三种GzmB+亚群(CD3+CD4+GzmB+、CD3+CD8+GzmB+、CD3+CD56+GzmB+)的比例更高(P=0.021、P=0.007、P=0.007)。CD3+CD8+GzmB+细胞/淋巴细胞比例的增加是TAK患者冠状动脉受累的独立危险因素(OR=4.990 [1.766-14.098],P=0.002)。此外,在TAK中,CD3+CD8+GzmB+细胞/淋巴细胞比率高的患者比比率低的患者有更高的MACE率(P=0.019)。我们的研究结果表明,CD8细胞衍生的Gzm B可能是TAK患者CAI和MACE的预测因子。针对CD3+CD8+GzmB+淋巴细胞或使用GzmB抑制剂可能是治疗TAK患者CAI的一种潜在治疗方法。
期刊介绍:
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.