Ab1296 Cd8 Cell-Derived Granzyme B May Be a Predictor for Coronary Artery Involvement and Mace in Takayasu Arteritis Patients

Background: Coronary artery involvement (CAI) is a special but not rare type in Takayasu arteritis (TAK) 1, 2. Granzyme B (GzmB) is a multifunctional protease in the immune system and coronary artery disease 3-5. However, its role in patients with TAK and CAI remains unclear. Objectives: In this study, we performed a systematic analysis to investigate the role of GzmB and its cells subsets in patients with TAK and coronary involvement. Methods: The study consisted of 105 TAK patients and 58 healthy controls.The percentages of different GzmB+ cells in blood samples was analyzed by flow cytometry. Results: We found that Age, Age at onset, BMI, disease duration month, hypertension and hyperlipidemia were significantly different among TAK patients with/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 kinds of GzmB+ subsets in lymphocytes (CD3+CD4+GzmB+, CD3+CD8+GzmB+, CD3+CD56+ GzmB+) were higher in TAK patients with CAI compared to non-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 with TAK (OR=4.990 1.766-14.098, P=0.002). Besides, patients with a high CD3+CD8+GzmB+cells/lymphocytes ratio had a higher MACE rate than those with the low ratio in TAK (P=0.019). Conclusion: Our results disclose the CD8 cell-derived Gzm B may be a predictor for CAI and MACE in TAK patients. Targeting CD3+CD8+GzmB+ lymphocytes or GzmB inhibitors could be a potential therapeutic approach for the treatment CAI of TAK. REFERENCES: 1 Yuan SM, Lin HZ: Coronary artery involvements in Takayasu arteritis: systematic review of reports. Gen Thorac Cardiovasc Surg 2020, 68(9):883-904. 2 Rav-Acha M, Plot L, Peled N, Amital H: Coronary involvement in Takayasu's arteritis. Autoimmun Rev 2007, 6(8):566-571. 3 Afonina IS, Cullen SP, Martin SJ: Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B. Immunol Rev 2010, 235:105-116. 4 Saito Y, Kondo H, Hojo Y: Granzyme B as a novel factor involved in cardiovascular diseases. J Cardiol 2011, 57(2):141-147. 5 Tsuru R, Kondo H, Hojo Y, Gama M, Mizuno O, Katsuki T, Shimada K, Kikuchi M, Yashiro T: Increased granzyme B production from peripheral blood mononuclear cells in patients with acute coronary syndrome. Heart 2008, 94(3):305-310. Acknowledgements: NIL. Disclosure of Interests: None declared.