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.