AB1283 ROLE OF IL-17A IN GIANT CELL ARTERITIS: POTENTIAL USEFULNESS AS A BIOMARKER FOR DISEASE ACTIVITY
Authors: A. González García, N. Bara, D. Lucena López, G. Starita Fajardo, I. García de la Torre, A. Vázquez Santos, G. Peralta Carrero, J. Jimenez Esteban, R. M. Fabregate Fuente, R. Ballester González, E. Rodríguez-Martín, P. De León Contreras, L. A. Viteri Noël, M. Fabregate
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Giant cell arteritis (GCA) is the most frequent vasculitis of the elderly. [1] Clinical management can be challenging due to the subjective nature of symptoms, difficulty in identifying flares, and loss of usefulness of biochemical parameters due to some of the treatments used (e.g., C-reactive protein and tocilizumab). Therefore, identifying new biomarkers applicable to clinical practice is an unmet need to support the management of GCA. In this regard, cytokines such as IL-17A or interferon, which are involved in the pathophysiology of the disease, may serve as useful diagnostic or activity disease biomarkers. [2] <h3>Objectives:</h3> We aimed to study the role of IL-17A in GCA and its potential usefulness as a biomarker for clinical practice. <h3>Methods:</h3> An observational cross-sectional study that included patients with definite diagnosis of GCA (ACR 1990 criteria) [1] was conducted in a systemic autoimmune disease unit from a tertiary hospital. We also included a non-GCA control cohort of patients from the internal medicine department matched for age (±5 years) and sex. Patients with other autoimmune/autoinflammatory diseases, active cancer, cardiovascular events, or major surgery within the previous 90 days were excluded from both groups. Demographic, laboratory, and clinical variables were collected, including the age-adjusted Charlson comorbidity index (aCCI; from 0 to 39 points). The GCA activity was characterized by the Birmingham Vasculitis Activity Score (BVAS; from 0 to 64 points). IL-17A levels were measured by flow cytometry (Cytometric Bead Array, BD) both in serum and peripheral blood mononuclear cells (PBMC) culture supernatant. The study was approved by the institutional Ethics Committee. The variables were described as frequencies (%) or median [interquartile range]. Comparisons were made using U-Mann-Whitney tests and linear associations were assessed using Pearson's r. Significance level was p&lt;0.05. IBM SPSS Statistics v24 was used for the analysis. <h3>Results:</h3> A total of n=15 patients with GCA and n=15 age- and gender-matched controls were enrolled. The median age was 80 [10] years in the GCA group and 82 [8] years in the control group, with 11/15 (73.3%) women in each group. There were no significant differences in comorbidity burden (aCCI: 6 [2] vs. 5 [4] points). Patients with GCA had a median BVAS activity of 1 [2] points. GCA patients showed significantly higher IL-17A values in PBMC supernatant compared to controls (37.9 [45.2] vs. 18.6 [14.9] pg/mL; p=0.042). However, differences in serum IL-17A levels did not reach significance (74.3 [41.0] vs. 58.0 [40.9] pg/mL; p=0.221). In turn, in GCA patients, serum IL-17A levels showed a positive linear correlation to disease activity measured by BVAS (r=0.762; p=0.001). <h3>Conclusion:</h3> Higher levels of IL-17A in the supernatant of PBMC cultures from GCA patients compared to controls suggest a potential role for this interleukin in the pathophysiology of the disease. Recent evidence has shown that IL-17, interferon γ and GM-CSF induce the differentiation of macrophage subpopulations involved in arterial wall destruction, neoangiogenesis and intimal hyperplasia, pathophysiological mechanisms of GCA [3]. Moreover, our study has shown that serum IL-17A could be useful as a biomarker for monitoring disease activity during clinical follow-up of GCA patients. <h3>REFERENCES:</h3> [1] Hunder GG, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990, 33:1122-1128. [2] Farina N, et al. Giant cell arteritis: Update on clinical manifestations, diagnosis, and management. Eur J Intern Med. 2023;107:17-26. [3] Greigert H, et al. New Insights into the Pathogenesis of Giant Cell Arteritis: Mechanisms Involved in Maintaining Vascular Inflammation. J Clin Med. 2022;11(10):2905. <h3>Acknowledgements:</h3> This project received partial funding from a research grant provided by Roche Farma, S.A. <h3>Disclosure of Interests:</h3> Andrés González García Roche Farma, S.A., Roche Farma, S.A.; Fresenius Kabi España, S.A., This project received partial funding from a research grant provided by Roche Farma, S.A., Nuria Bara: None declared, David Lucena López: None declared, Grisell Starita Fajardo: None declared, Iván García de la Torre: None declared, Almudena Vázquez Santos: None declared, Gracia Peralta Carrero: None declared, Judith Jimenez Esteban: None declared, Rosa María Fabregate Fuente: None declared, Rubén Ballester González: None declared, Eulalia Rodríguez-Martín: None declared, Patricia de León Contreras: None declared, Luis Adrián Viteri Noël: None declared, Martín Fabregate: None declared.