Pos0065 Characterization and Outcomes in the Novel Subgroups of 12 Cytokines in Takayasu Arteritis: A Data-Driven Cluster Analysis

Background: Takayasu arteritis (TA) is a rare autoimmune disease, which has varied clinical presentations with different disease progression[1]. There is growing need for clear biomarkers for TA[2]. At present, there is a wide range of research on cytokines, which vary greatly from patients to patients in TA[3,4]. It is important to scientifically explore the meaning behind different levels of cytokines and interpret their impact on outcomes and disease progression. Objectives: The research is to summarize subgroups characterized by cytokines in Takayasu arteritis and explore the differences in prognosis between subgroups. Methods: In this observational, longitudinal cohort study, serum cytokines (12 types) analyzed by flow cytometry were tested in 90 untreated TA cases. Disease duration, age of onset, elevated erythrocyte sedimentation rate (ESR), elevated c-reactive protein (CRP) and the levels of cytokines were analyzed by Twostep cluster analysis. Adverse events were defined as death, organ insufficiency and in-sent restenosis caused by the stenosis, occlusion and dilation of arteries due to TA. After the use of standard care therapy, relapse was defined as recurrence of active disease[5]. Refractory disease was defined as inability to attain disease remission despite the use of standard care therapy[5]. Kruskal-Wallis1-way (k samples) and Kaplan-Meier (Log-rank) were used to indicate the characterization and outcomes in subgroups. Results: In this study, 90 TA patients without treatment were divided into three subgroups, which were 34 (37.8%) in Cluster1, 10 (11.1%) in Cluster2 and 46 (51.1%) in Cluster3. The levels of CRP, ESR and IL-6 were significantly higher (20.18 [8.33,41.05]mg/L vs 1.52 [0.68,3.37]mg/L, p<0.001; 50.50 [31.25,77.25]mm/h vs 9.00 [6.00,15.75]mm/h, p<0.001; 15.37 [9.47,25.77]pg/ml vs 5.19 [3.25,8.64]pg/ml, p<0.001) in Cluster1 than in other subgroups. Cluster2 showed the higher levels of IL-1β, TNF-α, IFN-α (8.84 [3.76,13.11]pg/ml vs 1.49 [0.94,2.13]pg/ml, p<0.001; 8.52 [3.58,14.70]pg/ml vs 1.29 [0.90,2.10]pg/ml, p<0.001; 6.01 [5.21,12.63]pg/ml vs 1.23 [0.83,1.88]pg/ml, p<0.001). The levels of CRP, ESR and IL-6 were significantly lower in Cluster3 (1.58 [0.67,3.02]mg/L vs 16.77 [4.50,33.05]mg/L, p<0.001; 9.00 [5.75,14.00]mm/h vs 49.00 [27.25,70.50]mm/h, p<0.001; 4.80 [2.73,8.03]pg/ml vs 14.56 [8.82,22.41]pg/ml, p<0.001). In the comparison of NIH and ITAS.A, Cluster1 presented a more active disease than Cluster2 and 3 (3.00 [3.00,3.00] vs 2.00 [1.75,3.00] vs 2.00 [2.00,2.00], p<0.001; 10.50 [8.00,13.25] vs 7.00 [2.75,10.50] vs 5.50 [3.00,8.00], p<0.001). Adverse events, relapse and refractory disease occurred at the time of follow-up. There was a lower probability of the above outcomes in Cluster3 than Cluster2 and 1 (Log-rank p=0.010; Log-rank p<0.001; Log-rank p=0.014). Conclusion: The disease was more stable in Cluster3, which had the lower levels of CRP, ESR, IL-6. Additionally, there was a lower incidence of adverse events, relapse and refractory disease in Cluster3. Although the disease in Cluster2 wasn't as active as in Cluster1, the occurrence of outcomes was similar in the two subgroups. In clinical practice, elevated levels of cytokines should be noticed, which may predict different outcomes for patients. REFERENCES: [1] Quinn KA, Gribbons KB, Carette S, Cuthbertson D, Khalidi NA, Koening CL, et al. Patterns of clinical presentation in Takayasu's arteritis. Semin Arthritis Rheum. 2020;50(4):576-81. [2] Savioli B, Abdulahad WH, Brouwer E, Kallenberg CGM, de Souza AWS. Are cytokines and chemokines suitable biomarkers for Takayasu arteritis? Autoimmun Rev. 2017;16(10):1071-8. [3] Wen D, Feng L, Du X, Dong JZ, Ma CS. Biomarkers in Takayasu arteritis. Int J Cardiol. 2023;371:413-7. [4] Pan LL, Du J, Gao N, Liao H, Wan J, Ci WP, et al. IL-9-producing Th9 cells may participate in pathogenesis of Takayasu's arteritis. Clin Rheumatol. 2016;35(12):3031-6. [5] Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79(1):19-30. Acknowledgements: NIL. Disclosure of Interests: None declared.