Monocyte subsets and monocyte-related chemokines in Takayasu arteritis

Abstract

Background: The pathogenesis of Takayasu arteritis (TAK) is poorly understood. Although a macrophage-rich vessel wall granulomatous inflammation is a hallmark of TAK pathology, no previous studies have analyzed the monocytes’ role in the pathogenesis of the disease. This study aims to evaluate the distribution of monocyte subsets and the monocyte-related chemokines profile in the peripheral blood of TAK patients and age & sex matched healthy controls (HC). Methods: TAK patients were evaluated for current disease activity and current therapy. Monocyte subsets were identified by flow cytometry according to the surface expression of CD14 and CD16 as classical (CD14+CD16-), intermediate (CD14+CD16dim), and non-classical (CD14dimCD16high) in the peripheral blood. Multiplex Luminex assay was used to measure serum monocytes-related chemokines including CCL2, CCL3, CCL4, CCL5, CCL7, CXCL10 and CX3CL1. Results: Thirty-two consecutive TA patients and 30 HC were evaluated. TAK patients had a higher number of circulating intermediate monocytes compared to HC [25.01 cells x 106/L (16.7-52.0) vs. 17.2 cells x 106/L (9.2-25.3); p = 0.014]. Active disease was associated with monocytosis (p = 0.004) along with the increase of the classical (p = 0.003) and intermediate (p < 0.001) subsets compared to HC. No significant differences were found in the distribution of monocyte subsets between active disease and the remission state. Prednisone use reduced the percentage of non-classical monocytes (p = 0.011). TAK patients had lower CCL3 (p = 0.033) and CCL4 (p = 0.023) levels than HC, whereas CCL22 levels were higher in active TAK compared to the remission state (p = 0.008). Therapy with immunosuppressive agents or biologics did not impact serum chemokines, but glucocorticoids were associated with lower CXCL10 levels (p = 0.012). In TAK patients, CCL4 concentration correlated with the number of total monocytes (Rho = 0.489; p = 0.005) and classical and intermediate monocytes (Rho = 0.448; p = 0.010 and Rho = 0.412; p = 0.019) in the peripheral blood. Conclusions: TAK is associated with altered counts of monocyte subsets in the peripheral blood compared to HC and CCL22 is the chemokine with the strongest association with active disease in TAK.