AB1296 CD8 CELL-DERIVED GRANZYME B MAY BE A PREDICTOR FOR CORONARY ARTERY INVOLVEMENT AND MACE IN TAKAYASU ARTERITIS PATIENTS
Authors: L. Pan, T. LI
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> 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. <h3>Objectives:</h3> 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. <h3>Methods:</h3> The study consisted of 105 TAK patients and 58 healthy controls.The percentages of different GzmB<sup>+</sup> cells in blood samples was analyzed by flow cytometry. <h3>Results:</h3> 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<sup>+</sup>CD8<sup>+</sup>cells (P=0.001) and CD3<sup>+</sup>CD4<sup>+</sup>cells (P=0.000) in GzmB<sup>+</sup> cells were significantly increased while the proportion of CD3<sup>-</sup>CD56<sup>+</sup>cells (P=0.001) in GzmB<sup>+</sup> cells was decreased in TAK patients. The proportions of three kinds of GzmB<sup>+</sup> subsets in lymphocytes (CD3<sup>+</sup>CD4<sup>+</sup>GzmB<sup>+</sup>, CD3<sup>+</sup>CD8<sup>+</sup>GzmB<sup>+</sup>, CD3<sup>+</sup>CD56<sup>+</sup> GzmB<sup>+</sup>) 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<sup>+</sup>CD8<sup>+</sup>GzmB<sup>+</sup>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<sup>+</sup>CD8<sup>+</sup>GzmB<sup>+</sup>cells/lymphocytes ratio had a higher MACE rate than those with the low ratio in TAK (P=0.019). <h3>Conclusion:</h3> Our results disclose the CD8 cell-derived Gzm B may be a predictor for CAI and MACE in TAK patients. Targeting CD3<sup>+</sup>CD8<sup>+</sup>GzmB<sup>+</sup> lymphocytes or GzmB inhibitors could be a potential therapeutic approach for the treatment CAI of TAK. <h3>REFERENCES:</h3> [1] Yuan SM, Lin HZ: Coronary artery involvements in Takayasu arteritis: systematic review of reports. <i>Gen Thorac Cardiovasc Surg</i> 2020, 68(9):883-904. [2] Rav-Acha M, Plot L, Peled N, Amital H: Coronary involvement in Takayasu's arteritis. <i>Autoimmun Rev</i> 2007, 6(8):566-571. [3] Afonina IS, Cullen SP, Martin SJ: Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B. <i>Immunol Rev</i> 2010, 235:105-116. [4] Saito Y, Kondo H, Hojo Y: Granzyme B as a novel factor involved in cardiovascular diseases. <i>J Cardiol</i> 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. <i>Heart</i> 2008, 94(3):305-310. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>