Serum Biomarker Profile Explains Heterogenity in Patients With Takayasu Arteritis: An Exploratory Analysis

Abstract

Abstract The clinical presentation of patients with Takayasu arteritis (TAK), a large vessel vasculitis, is heterogenous and absence on an ideal biomarker renders assessment of disease activity difficult. In the present study we determined the biomarker profile of patients with TAK and subclassified them based on the same. Methods: Serum of consecutive patients with TAK and 36 controls were subjected to bead-based-multiplex assay or ELISA to quantify cytokines or chemokines or growth factors representing various pathophysiological pathways in TAK. The concentration of analytes between patients and controls and among various subsets of patients were compared. Unbiased clustering of patients was performed by dimensionality reduction methods and correlation networks were constructed. The surgical arterial biopsies of a subset of patients were examined for the extent of inflammation, fibrosis and myxomatous changes in arterial wall and the changes were correlated with cytokine concentration. Results: 85 patients with TAK [66 females, mean age: 28.8 ± 8.9 years, symptom duration of 24 months (IQR: 8–48 months)] and 36 controls were recruited. Levels of B cell antigen (BCA-1) and Pentraxin-3 were higher in patients than controls after applying correction for multiple testing (p < 0.02 for both). IL18 levels were highest in type 5 subtype (p = 0.015) while angiopoietin-2 and BCA-1 levels were highest in type 4 disease (p = 0.015, 0.003 and 0.009 respectively). The level of angiopoietin-2 was higher in patients with active disease (n = 52) than stable disease at baseline (p = 0.007) while IL6 and MMP-2 were paradoxically lower in patients with active disease (p = 0.029 and 0.021 respectively). Serum IL18 and IL2Rα levels trended to correlate positively with intensity of inflammation in the studied samples of aortic tissues. Among treatment naïve patients, those with lower concentration serum IL15, IFNγ and IL12p70 separated into one cluster. The angiogenic factors, MMP-9 and pentraxin-3 demonstrated interconnectedness in patients with active disease and not in those with stable disease. Conclusions: Patients with TAK have varied biomarker profile that depends on angiographic type and intensity of inflammation. While BCA-1 and Pentraxin levels were higher in TAK as compared with controls, angiopoietin-2, Il-6 and MMP-2 levels differentiated active from stable TAK. The biomarkers interconnected among each other differently in active and stable patients.