Pos0799 biomarker changes in takayasu arteritis after tofacitinib treatment and the molecular signature associated with disease characteristics

Background Takayasu’s arteritis (TAK) is a chronic, non-specific, granulomatous macrovasculitis and its pathogenesis is still unclear. The increasing evidence indicated that multiple pathological process involved in the development of TAK. According to previous reports, multiple biomarkers representative different pathological process (1-3), However, which biomarker can closely reflect disease activity or vascular changes and whether these abnormal processes can be prevented by current therapies remained unknown. Objectives To analyze changes of serum cytokine, chemokine, and growth factor profiles in patients with Takayasu arteritis (TAK) after tofacitinib treatment and explore potential molecular signatures related with various disease characteristics Methods Seventeen patients from a TAK cohort treated with tofacitinib and 12 healthy controls were recruited in this study. Potential biomarkers with TAK including cytokines, MMPs, chemokines and growth factors were detected in these patients (0, 6, 12 months) and healthy controls. Molecular changes, disease activity, disease remission, and vascular imaging changes were analyzed in these patients after treatment. Furthermore, molecule signatures associated with these clinical features/outcomes were explored via radar plot and correlation analysis. Results At baseline, all the patients were in active status. Meanwhile, patients’ cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factor (VEGF) and MMP9 were significantly higher than those of healthy controls (all p<0.05), while FGF-2 was significantly lower in patients with TAK (p=0.02). After treatment, 94.12% of patients achieved complete remission at 6 and 12 months; patients’ ESR and CRP levels were significantly reduced at 6 months (p=0.02, p=0.046 respectively); vascular improvement were observed in 6 (35.29%) patients at 12 months. With regards to these molecules, IL-10 was increased at 6 months compared with its baseline level (p=0.007). No changes were observed in other cytokines, chemokines, or growth factors. Besides, the radar plot demonstrated that PTX3 was closely correlated with disease activity. In addition, patients with vascular imaging improvement had relatively higher baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively), lower CCL22, FGF, and PDGF-AB levels (p=0.056, p=0.06 and p=0.08 respectively) compared with patients without it. Conclusion Multiple molecules representative different pathological mechanism participated in the pathogenesis of TAK. PTX3 was a prominent marker for disease activity, and CCL22 may have a predictive value for vascular imaging changes. References [1]Dagna L, Salvo F, Tiraboschi M, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med . 2011;155(7):425-433. doi:10.7326/0003-4819-155-7-201110040-00005 [2]Sun Y, Kong X, Wu S, et al. YKL-40 as a new biomarker of disease activity in Takayasu arteritis. Int J Cardiol . 2019; 293: 231-237 [3]Dong H, Zhang Y, Zou Y, et al. Elevated chemokines concentration is associated with disease activity in Takayasu arteritis. Cytokine . 2021; 143: 155515 Disclosure of Interests None declared