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Xiaojuan Dai,1 Jinghua Wang,1 Xiao Zhang,1 Li Wang,1 Sifan Wu,1 Huiyong Chen,1 Ying Sun,1 Lili Ma,1 Lingying Ma,1 Xiufang Kong,1 Lindi Jiang1,2 1Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Lindi Jiang; Xiufang Kong, Email zsh-rheum@hotmail.com; kongxiufang2007@163.comObjective: This study aimed to analyze biomarker changes in patients with TAK following treatment with glucocorticoids (GCs) and tofacitinib (TOF).Methods: Seventeen patients from a prospective TAK cohort treated with GCs and TOF and 12 healthy individuals were recruited. TAK associated cytokines, chemokines, growth factors, and MMPs were analyzed in these patients before and after GCs and TOF treatment, and healthy controls. Molecular signatures associated with clinical features were evaluated.Results: Patients’ cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factors (VEGF), and MMP9 levels were significantly higher at baseline (all p < 0.05), while patients’ FGF-2 levels were significantly lower (p = 0.02). After treatment, IL-10 was significantly increased at 6 months (p=0.007), and inflammatory cytokines such as PTX3, IL-6 demonstrated a downward trend. Patients without vascular occlusion had higher baseline CCL22 levels than patients with it (p = 0.05), which remained persistently higher after treatment. Radar plot analysis demonstrated that PTX3 was closely correlated with disease activity. In addition, patients without imaging improvement had relatively higher baseline levels of CCL22, FGF-2, and PDGF-AB (p = 0.056, p = 0.06 and p = 0.08 respectively) and lower baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively) compared with patients without it.Conclusion: GCs and TOF are effective in decreasing inflammatory molecules but have limited efficacy in

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.