Pos0760 the Potential Role of Cell-Death Mechanisms in the Pathogenesis of FMF Attacks

Background: The potential role of cell-death mechanisms in the pathogenesis of FMF attacks [1-2]. Objectives: The aim of this study is to demonstrate the role of natural killer (NK) cell sandcytotoxic T cells, which are crucial components of th innateimmunesystem, in the on set and resolution of AAA attacks. Additionally, the objective is to identify the differences between AAA patient sand PFAPA patients, determine the factors triggering the disease, and uncover potential targeted treatment options. Methods: Blood samples were collected from each patients during attack andattack-freeperiod. After giving information and taking the onset of patient sand their parents, an extra blood sample of a tube with EDTA was taken and transferred to the Hacettepe University Translational Medical Laboratory of Pediatric Romatology Unit. Here, the samples were centrifuged at 4000rpm for 10 minutes at room temperature, the plasma were separated and stored at -80C. The demographics, clinical findings and laboratory test results of these patients were also recorded. Experimental studies were carried out at the Hacettepe University Translational Medical Laboratory, Pediatric Romatology Unit. Results: 25 FMF (48% female), 10 PFAPA (40% female) patients and 10 healthy control (40% female) were included for this study. The median age of FMF patients, PFAPA patients and heatlhy controls were 7.1(5.7) years, 2.9(2) years and 11.5(7.5) years, respectively. Compared with the attack-free period, IL-6 levels were found to be increased in both FMF patients (attack 85.2(125.8) pg/mL attack-free 19.9(15.09) pg/mL; p=0.001) and in PFAPA patients (attack 69.6(78.8) pg/mL attack-free 20.1(20.3) pg/mL; p=0.01)during the attack period. However, IL 4 (FMF attack89.3(246.6) pg/mL attack-free 29.6(15.6) pg/mL; p=0.025) and IL-10 (FMF attack 25.7(48.19) pg/mL attack-free 116.4(10.7) pg/mL; p=0.039) levels were foundto be statistically significantly increased only in FMF patients. Interms of IL-2, IL-17A and TNF alpha, nosignificantdifferencewasfoundbetweenattack-freeandattackperiod in both FMF and PFAPA patients. After wards, we examined the components of the apoptosis and pyroptosis pathway in which NK and cytotoxic T cells act an effective role. In FMF patients, sFasL (attack 93.4(86.1) pg/mL attack-free 55.1(28.1) pg/mL; p=0,035) and Granzyme A (attack 2572.9(3332.4) pg/mL attack-free 1354.7(510.8) pg/mL; p=0.038) levels increased significantly during the attack period and decreased to the comparable levels with the healthy controls during the attack-free period. This increase was not seen in PFAPA patiens, who had similar levels with the healthy control group both in the attack and attack-free period. Granzyme B (attack 3576.2(2418.6) pg/mL attack-free 2304.6(1960.7) pg/mL; p=0,145) and Perforin (attack 4488.4(6470.6) pg/mLvsattack-free 4605.9(2998.8) pg/mL; p=0,203) levels were also increased during the attack period of FMF patients, but these differences were not statistically significant. During the attack period of FMF patients sFasL, Granzyme A, Granzyme B and Perforin levels were closely correlated with each other. Conclusion: As a result, we showed for the first time that Granzyme A levels are increased during the attac kperiod in FMF patients. In our study, together with the Granzyme A, FasL levels were also found to be increased significantly and which were normalized in the after attac kperiod. With these results, it is shown that the pyroptosis pathway can be activated independently of the caspase system. REFERENCES: [1] Sag E, Bilginer Y, Ozen S. Autoinflammatory Diseases with Periodic Fevers. Curr Rheumatol Rep. 2017 Jul;19(7):41. doi: 10.1007/s11926-017-0670-8. PMID: 28631068. [2] Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, Wang Y, Li D, Liu W, Zhang Y, Shen L, Han W, Shen L, Ding J, Shao F. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020 May 29;368(6494):eaaz7548. doi: 10.1126/science.aaz7548. Epub 2020 Apr 16. PMID: 32299851. Acknowledgements: NIL. Disclosure of Interests: None declared.