Li Taotao, Gao Na, Du Juan, Zhao Limin, Yang Shiyu, Zhang Yaxin, Zhu Junming, Hu Haiou, Qiao Zhiyu, Cui Wei, Pan Lili
Department of Rheumatology and Immunology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China.
Beijing Institute of Heart, Lung and Vessel disease, Capital Medical University Affiliated Anzhen Hospital, Beijing, China.
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxae095.
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, body mass index, 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 with 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 major adverse cardiovascular events 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 major adverse cardiovascular events 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）是大动脉炎（TAK）一种特殊但并不罕见的表现。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，其在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。该研究纳入了105例TAK患者和58例健康对照。通过流式细胞术分析血样中不同GzmB +细胞的百分比。我们发现，有和没有CAI的TAK患者在年龄、发病年龄、体重指数、病程月数、高血压和高脂血症方面存在显著差异（P = 0.000，P = 0.038，P = 0.003，P = 0.031，P = 0.039，P = 0.000）。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 +细胞的比例（P = 0.001）降低。与没有CAI的TAK患者相比，有CAI的TAK患者淋巴细胞中三种类型的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，TAK患者中CD3 + CD8 + GzmB +细胞/淋巴细胞比例高的患者主要不良心血管事件发生率高于比例低的患者（P = 0.019）。我们的结果表明，CD8细胞衍生型Gzm B可能是TAK患者CAI和主要不良心血管事件的预测指标。靶向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。
