Lijuan Liu

Treg cells play an important role in the induction of autoimmune tolerance, and their ability of antigen recognition and regulation is determined by the receptor (TCR). TCR diversity determines the autoimmune responses in RA and is closely associated with autoimmune diseases prognosis and prevention. Previous studies have found that there is immunosenescence in RA, that is, the decrease of the number of naïve CD4 ⁺ T cells and the reduction of TCR repertoire diversity. High disease activity is an independent risk factor for RA. We speculate that high disease activity is related to immunosenescence—the decline of adaptive immune function and a chronic inflammation, but its biological mechanism is still unclear and needs to be further elucidated. In this study, high-throughput Immuno-Seq sequencing and flow cytometry were used to compare normal subjects and RA patients, as well as RA patients whose disease activity changed to clinical remission after standard treatment. It was found that high disease activity not only led to a decrease in the number of naïve Treg cells, but also led to a decrease in the diversity of Treg cell receptor repertoire, weakening their ability to recognize self-antigens and induce immune tolerance, leading to the occurrence and development of RA. Besides, these characteristics of the TCR repertoire, particularly the disease activity related clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.

Background: Rheumatoid arthritis (RA) is a common chronic autoimmune disease that seriously affects the quality of life of patients because of damage to joints. Presently, RA is mainly treated with disease-modifying antirheumatic drugs (DMARDs) or biological agents; however, they offer limited efficacy in some patients. Therefore, additional therapeutic strategies need to be developed. Yishen Tongbi decoction is a traditional Chinese medicine formulation widely used to treat RA in China. However, currently, there is insufficient evidence to recommend its use for the treatment of RA. Therefore, we aim to verify the efficacy of Yishen Tongbi decoction to treat RA by a noninferiority trial, and to provide a basis for its use with a full-scale clinical trial.Methods/design: One hundred eligible patients with RA will be randomized into two groups of 50 patients. One group will receive Yishen Tongbi decoction and placebo replacing methotrexate (MTX), while the other group will receive MTX and placebo replacing Yishen Tongbi decoction. Patient’s whose visual analogue scale score for pain is greater than 40 mm will be administered nonsteroidal anti-inflammatory drugs (such as enteric-coated diclofenac sodium, 25 mg three times a day); administration of all medications will be recorded. The clinical indicators of patients and their disease activity will be assessed at baseline and at 4, 12 and 24 weeks after treatment initiation. The primary outcome of efficacy will be the proportion of patients who demonstrate a favourable response based on their Clinical Disease Activity Index score at 24 weeks after treatment. All adverse events will be reported.Discussion: Traditional Chinese medicine theory and modern western medicine research have identified the efficacy of Yishen Tongbi decoction to treat RA. Previous clinical observation and efficacy trials of Yishen Tongbi decoction in animal models for the treatment of RA has demonstrated significant effect. Because of the potential benefits of Yishen Tongbi decoction in the treatment of patients with RA, we designed this double-blind, prospective, randomized controlled trial; the results and conclusions of the trail will be published after the completion of the study.Trial registration: Chinese Clinical Trials Registry,ChiCTR1900024902. Registered on 3 August 2019.