Analysis of proinflammatory cytokine responses in Takayasu arteritis
Rabia Deniz1,2,3
, Aysın Tulunay-Virlan4, Filiz Ture Ozdemir4, Ali Ugur Unal2, Gulsen Ozen2, Fatma Alibaz-Oner2, Imren Aydin-Tatli4, Haner Direskeneli2
1Department of Medical Biology and Genetics, Marmara University Faculty of Medicine, İstanbul, Türkiye
2Department of Internal Medicine, Division of Rheumatology, Marmara University Faculty of Medicine, İstanbul, Türkiye
3Department of Rheumatology, University of Health Sciences, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye
4Department of Immunology, Marmara University Faculty of Medicine, İstanbul, Türkiye
Keywords: Adaptive immunity, interferon-gamma, interleukin-17, Takayasu arteritis, T helper 17 cells.
Abstract
Objectives: This study aimed to investigate the expression of proinflammatory cytokines under long-term T helper (Th) 17 cell inducing conditions in Takayasu arteritis (TAK), a granulomatous vasculitis with adaptive immune responses.
Patients and methods: This cross-sectional study was conducted between May 2014 and April 2017. Peripheral blood mononuclear cells from 25 patients (23 females, 2 males; mean age: 42.7±15.5 years; range, 20 to 69 years) with TAK and 25 healthy controls (HCs; 11 females, 14 males; mean age: 39.1±9.3 years; range, 21 to 64 years) were cultured in Th17 cell-inducing conditions for six days. Cultured cells were stained with conjugated monoclonal antibodies to determine the intracellular cytokine secretion by flow cytometry. Supernatant samples were measured with sandwich enzyme-linked immunosorbent assay for interferon-gamma (IFN-γ), interleukin (IL)-17, IL-7, IL-21, and IL-22 levels.
Results: Under Th17 cell-inducing conditions, IFN-γ secretion was significantly higher in the TAK group compared to HCs (p<0.005). Unstimulated serum cytokine levels showed no differences between the TAK and HC groups, except for IL-7. Both IL-17 and IFN-γ secretion showed significant increases in TAK and IL-17 secretion in HCs in comparison of unstimulated and stimulated samples for each individual (p values, 0.022, 0.005, and 0.016, respectively). The production of IL-17 and IFN-γ by CD4+ , CD8+ , and γδ+ T cells and B cells was not found to be significantly different between TAK patients and HCs. No differences were observed between the subgroups of TAK according to disease activity or treatment in IL-17 and IFN-γ production.
Conclusion: This study supports cell-mediated cytotoxicity as the main pathogenetic mechanism of TAK. T cells express higher levels of IFN-γ in TAK but not IL-17. Supernatant analysis indicated significantly higher IFN-γ production, which significantly increased after induction, suggesting the contribution of different inflammatory cells (probably CD8+ and γδ+ T cells) to IFN-γ production in TAK.
Citation: Deniz R, Tulunay-Virlan A, Ture Ozdemir F, Unal AU, Ozen G, Alibaz-Oner F, et al. Analysis of proinflammatory cytokine responses in Takayasu arteritis. Arch Rheumatol 2024;39(4):598-606. doi: 10.46497/ ArchRheumatol.2024.10790.