Ultrasound inflammatory parameters and Treg/Th17 cell profiles in established rheumatoid arthritis

Abstract

Background: Imbalance and disfuntion in regulatory T-cells (Tregs) and IL-17 producer lymphocytes (Th17) have been implicated in the pathogenesis of rheumatoid arthritis (RA). Gray scale synovial proliferation (GS), power Doppler signal (pD) and bone erosions seen on high resolution muskuloskeletal ultrasound (MSUS) are hallmarks of destructive articular disease. Objective: To evaluate the association of peripheral Tregs and Th17 with MSUS findings in RA. Methods: RA patients (1987 ACR criteria) treated with disease-modifying antirheumatic drugs (DMARDs) were included. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate regulatory FoxP3+ T cells and IL-17+ cells. MSUS (MyLab 60, Esaote, Genova, Italy, linear probe 6-18 MHz) was performed on hand joints, and a 10-joint US score was calculated for each patient. Results: Data on lymphocytes subsets were avaiable for 90 patients. The majority of patients were Caucasian women with a median disease duration of 6 years (interquartile range: 2-13 years). Mean DAS28 was 4.28 (SD ± 1.64) and mean HAQ score was 1.11 (SD ± 0.83). There was no significant correlation of 10-joint GS score (rS = 0.122, 95% CI: − 0.124 to 0.336, P = 0.254) and 10-joint pD score (rS = 0.056, 95% CI: − 0.180 to 0.273, P = 0.602) with the mean percentage of peripheral Treg cells. Also, 10-joint GS score (rS = 0.083, 95% CI: − 0.125 to 0.302, P = 0.438) and 10-joint pD score 10 (rS = − 0.060, 95% CI: − 0.271 to 0.150, P = 0.575); did not correlate to Th17 profile. No association of bone erosions on MSUS with Treg and Th17 profiles (P = 0.831 and P = 0.632, respectively) was observed. Conclusion: In this first study addressing MSUS features and lymphocytes subtypes in established RA, data did not support an association of circulating Tregs and Th17 lymphocytes with inflammatory and structural damage findings on MSUS.

Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases

“…In recent years, bone immune regulation has become a hot topic in research on bone metabolic diseases ( 74 ). Research has found that bone immunity has a destructive effect ( 75 ), and bone immune disorders induced by Th17 cells, Tregs, and related cytokines are important triggers for the development of RA and PMOP ( 17 , 76 ) Many studies have shown that the proportion of Th17 cells in the serum and synovium of patients with RA and collagen-induced arthritis (CIA) rats is far higher than that of Treg cells, however, inhibiting Th17 cells and upregulating Treg cells can alleviate arthritis and bone destruction ( 77 , 78 ), indicating that regulating the Th17/Treg cell balance may be important for the treatment of RA. In addition, some studies have confirmed that in patients with PMOP and ovariectomized (OVX) mice, Th17 cells and their related cytokines, such as IL-17, TNF-α, and IL-6, increased, Treg cells and their related anti-inflammatory factors decreased, OC-mediated bone resorption and OB-mediated bone formation were out of balance, the Th17/Treg ratio increased, and the bone remodelling process was worsened.…”