A comprehensive profile of chemokines in the peripheral blood and vascular tissue of patients with Takayasu arteritis.

BACKGROUND

Takayasu arteritis (TAK) is a chronic granulomatous large vessel vasculitis with multiple immune cells involved. Chemokines play critical roles in recruitment and activation of immune cells. This study aimed to investigate chemokine profile in the peripheral blood and vascular tissue of patients with TAK.

METHODS

A total of 58 patients with TAK and 53 healthy controls were enrolled. Chemokine array assay was performed in five patients with TAK and three controls. Chemokines with higher levels were preliminarily validated in 20 patients and controls. The validated chemokines were further confirmed in another group of samples with 25 patients and 25 controls. Their expression and distribution were also examined in vascular tissue from 8 patients and 5 controls. Correlations between these chemokines and peripheral immune cells, cytokines, and disease activity parameters were analyzed. Their serum changes were also investigated in these 45 patients after glucocorticoids and immunosuppressive treatment.

RESULTS

Patients and controls were age and sex-matched. Twelve higher chemokines and 4 lower chemokines were found based on the chemokine array. After validation, increase of 5 chemokines were confirmed in patients with TAK, including CCL22, RANTES, CXCL16, CXCL11, and IL-16. Their expressions were also increased in vascular tissue of patients with TAK. In addition, levels of RANTES and IL-16 were positively correlated with peripheral CD3CD4 T cell numbers. Close localization of CCL22, CXCL11, or IL-16 with inflammatory cells was also observed in TAK vascular tissue. No correlations were found between these chemokines and cytokines (IL-6, IL-17, IFN-γ) or inflammatory parameters (ESR, CRP). No differences were observed regarding with these chemokines between active and inactive patients. After treatment, increase of CCL22 and decrease of RANTES and CXCL16 were found, while no changes were showed in levels of CXCL11 and IL-16.

CONCLUSIONS

CCL22, RANTES, CXCL16, CXCL11, and IL-16 were identified as the major chemokines involved in the recruitment of immune cells in the vascular tissue of patients with TAK. Additionally, the persistently high levels of CCL22, CXCL11, and IL-16 observed after treatment indicate their role in vascular chronic inflammation or fibrosis and demonstrate the need for developing more efficacious treatment options.