324. Changes of molecular signature in TAK with tofacitinib treatment and their correlation with disease characteristics
Creators: name: Xiaojuan Dai1
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background/ Objectives: </strong>To analyze changes of serum cytokine, chemokine, and growth factor iles in Takayasu arteritis (TAK) patients treated with tofacitinib and explore molecular signatures related with various disease characteristics. <strong>Methods:</strong> Seventeen patients with TAK and 12 age-and gender matched healthy controls were recruited in this study. These patients were included from an ongoing prospective TAK cohort treated with glucocorticoids and tofacitinib. Patients’ disease activity, disease severity and imaging changes were evaluated at baseline, 6 and 12 months after treatment. Routine inflammatory parameters erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also collected. Cytokines (PTX3, IL-6, IFN-r, IL-17, TNF-a, YKL40, IL-10), chemokines (IL-16, CCL22, CCL2, CCL5), MMPs (MMP1, MMP2, MMP3), and growth factors (VEGF, FGF, PDGF) were detected in these patients at baseline, 6 and 12 months and healthy controls. Patients’ baseline molecules were compared with that of healthy controls and their changes after treatment were analyzed at 6 and 12 months. In addition, correlations among these molecules or between these molecules and ESR or CRP were analyzed. Furthermore, molecule signatures were explored via radar plot to assess their relationship with disease activity, disease severity, and vascular imaging changes. <strong>Results:</strong> At baseline, all the patients were in active status according to NIH disease activity criteria, and 10(58.82%)were assessed as severe disease. After treatment, 1(5.88%), and 1(5.88%)patients were in active disease at 6 and 12 months. After 12 months’ treatment, 1 (5.88%) patient presented vascular imaging progression, while 6 (35.29%) patients’ vascular lesions were improved. Patients’ ESR and CRP levels were significantly reduced at 6 months. (p =0.024, p=0.0467 respectively). In ter of those molecules, 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&lt;0.05), while FGF was significantly lower in patients with TAK (p=0.02). The correlation analysis showed that PTX3 was correlated with CRP (p=0.01, r=0.60) and IL-6 (p=0.006, r=0.66). After treatment, IL-10 was significantly increased at 6 months compared with its baseline level (p= 0.0069). Levels of TNF-a was decreased at 12m compared with its level at 6 months (p=0.034). IFN-γ also showed an decrease trend at 12 months in contrast to its level at 6 months (p=0.076 ). The radar plot of molecules in patients with different NIH score demonstrated that PTX3 was closely correlated with disease activity. By comparing these molecular levels at baseline between patients with and without imaging improvment, patients with imaging improvement had relative higher TNFα, ESR and CRP levels (p=0.04, p=0.056, p=0.07 respectively) and relative lower CCL22, FGF and PDGF levels (p=0.056, p=0.06, p=0.08 respectively). <strong>Conclusions:</strong> Multiple molecules representative different pathological mechanism participated in the pathogenesis of TAK. Tofaticinib was not sufficient to inhibit the expression of these pathogenic molecules. PTX3 was a prominent marker for disease activity, and CCL22 may have a predictive value for vascular imaging changes. <strong>Disclosures:</strong> none