Lupus nephritis(LN)is a common and severe complication of systemic lupus erythematosus(SLE).Approximately 10%of patients with severe LN may progress to end-stage renal disease within 10 years of diagnosis,accompanied by high morbidity and mortality.In the field of treatment,glucocorticoids,antimalarials and other conventional agents have remained the mainstay since the early days,and new therapies emerged slowly until belimumab was approved.In recent years,there has been renewed progress in the research and treatment of SLE and LN,with a series of innovative therapies emerging,including biologics such as anti-B cell-activating factor antibodies,anti-CD20 antibodies,anti-CD40 antibodies,and anti-interferon antibodies,as well as small molecule kinase inhibitors.These developments have shifted treatment strategies towards more individualized and precise approaches.However,despite the expanding array of treatment options,many therapeutic needs remain inadequately met.This paper summarizes recent clinical trials and post-hoc analyses of LN,highlighting advances in promising therapeutic strategies.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. There are still many limitations and individual differences in the treatment based on glucocorticoids and immunosuppressants. In recent years, more and more studies have shown that the combination of traditional Chinese medicine in the treatment of SLE has the advantages of good efficacy, low adverse reactions, and high safety. However, the exact regulatory mechanism and combined traditional Chinese medicine in the treatment of SLE are still unclear. This paper reviews the research on the mechanism of traditional Chinese medicine in the treatment of SLE from metabonomic, immune cells, lymphocyte factors and apoptosis, etc, provides ideas for exploring the mechanism of traditional Chinese medicine in the treatment of SLE with modern methods.

Interleukin-17/genetics*

In recent years, with the continuous in-depth research on the pathogenesis of rheumatism and the rapid development of biopharmaceutical technology, the development of targeted drugs for rheumatism is in full swing. In order to better standardize the diagnosis and treatment of rheumatism and the rational application of targeted drugs, the Chinese Rheumatology Association will introduce the targeted drugs for rheumatism that have been approved by the China National Medical Products Administration so far, and provide clinicians with standardized diagnosis and treatment reference.

Immunization with regulatory T cell (Treg) epitope peptides to activate and induce Tregs, by which to suppress pathological autoimmune responses and reconstitute a new homeostasis, is a promising therapeutic regimen for autoimmune rheumatic diseases. However, it is usually hard to induce potent peptide-specific immune responses in vivo with small molecular peptides. Bacterial flagellin is one of the agonists triggering innate immune responses. When used as carrier, it shows strong adjuvant activity to its conjugated antigens. In some particular situations, bacterial flagellin can also activate and induce Tregs. Thus if Treg epitope peptides are covalently conjugated to a bacterial flagellin, the conjugates should be able to effectively enhance the Treg-based immune responses via flagellin itself and the adjuvanticity of flagellin to Treg epitope peptides, and thereby enhance the immunotherapeutic effects on autoimmune rheumatic diseases.

Although many drugs and therapeutic strategies have been developed for rheumatoid arthritis (RA) treatment, numerous patients with RA fail to respond to currently available agents. In this review, we provide an overview of the complexity of this autoimmune disease by showing the rapidly increasing number of genes associated with RA.We then systematically review various factors that have a predictive value (predictors) for the response to different drugs in RA treatment, especially recent advances. These predictors include but are certainly not limited to genetic variations, clinical factors, and demographic factors. However, no clinical application is currently available. This review also describes the challenges in treating patients with RA and the need for personalized medicine. At the end of this review, we discuss possible strategies to enhance the prediction of drug responsiveness in patients with RA.

Objective To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) and joint ultrasonography in assessing the activity of rheumatoid arthritis (RA) by comparing MMP-3 level and the ultrasonic 7 joints (US7) score in RA patients.Methods Serum MMP-3 level and US7 score were measured in 133 RA patients by immune turbidity and Doppler ultrasound.Synchronous 53 healthy subjects were recruited as controls.Clinical data were collected.Erythrocyte sedimentation rate (ESR),serum level of anti-cyclic citrullinated peptide (CCP) antibody,health assessment questionnaire (HAQ) and disease activity score 28 (DAS28) were measured.The level of disease activity is interpreted as remission(DAS28 ＜2.6),low(DAS 28≥2.6-＜3.2),moderate(DAS 28≥3.2-＜5.1),high(DAS28≥5.1).The discriminating validity of MMP-3 and US7 score in disease was evaluated using receiver operating characteristic (ROC) curve analysis with DAS28 as the reference standard.Results Compared with that in healthy controls [35.20(25.90,48.90) μg/L] and remission patients[33.40(22.60,678.40) μg/L],the MMP-3 level in moderate [105.1 (61.70,172.70) μg/L] and high [363.1 (161.50,475.90) μg/L]groups increased dramatically.US7 score in patients with high disease activity was significantly higher than that in other groups.The level of MMP-3 was significantly correlated with DAS28,HAQ,US7 score,yet did not have correlation with anti-CCP antibody.Serum level of MMP-3 was positively correlated with US7 score (r =0.566,P ＜ 0.001).In evaluating the disease activity,US7 score combined with MMP-3 (AUC 0.863 2) was not superior to MMP-3 alone (AUC 0.854 3),but significantly better than single US7 score (AUC 0.7643,P ＜ 0.05).Conclusions MMP-3 is an effective and simple index in evaluating RA disease activity.The combination of MMP-3 and US7 score does not further improve the efficacy to evaluate disease activity than MMP-3 alone in patients with RA.

Objective To explore the value of ultrasonographic US7 scores in clinical evaluation of rheumatoid arthritis (RA) patients,by comparing US7 scores in RA patients with different disease activities.Methods US7 scores of 133 patients in different active stages of RA were measured and evaluated by using color Doppler ultrasonography.Then,its relationship with erythrocyte sedimentation rate (ESR),anti-CCP antibody,HAQ,DAS28 and other indicators was analyzed statistically.Results (1) Significant differences could be seen in the US7 scores of the patients with severe active RA,as compared with those of the patients with stable,mild and moderate active RA(7.0 VS 0,7.0 VS 1.0,7.0 VS 2.0,7.0 VS 3.0) (P ＜0.05).Ultrasonographic US7 scores were positively correlated with DAS28 and HAQ.(2) US7 revealed that synovitis gray scale (GS) scores accounted for the highest (63.1％),while synovitis blood flow signal (PD) scores,tenosynovitis GS scores,tenosynovitis PD scores and bone destruction scores accounted for (18.3％),(7.2％),(4.3％) and (6.9％) respectively.The most easily affected site in synovitis was dorsal wrist synovium (82.7％),followed by volar MCP Ⅱ synovium (53.3％).The most easily affected site in tenosynovitis was the dorsal wrist joint (15.8％),followed by the dorsal MCPⅡ (15.7％).In bone destruction,the most easily affected site was ulnar MTPV (33.8％),with radialis MCPⅡ (24.1％) being the second.Conclusions Ultrasonographic US7 scores could effectively reflect the disease activity in RA patients,and it was of good value to those with severe active RA.In US7 scores,the rate of synovitis was significantly higher than those of tenosynovitis and bone destruction,and the most easily affected site was dorsal wrist joint and palmar MCPⅡ.Clinically,more attention should be paid to the changes in these two joints.

Objective To explore the value of ultrasonographic US7 scores in clinical evaluation of rheumatoid arthritis (RA) patients,by comparing US7 scores in RA patients with different disease activities.Methods US7 scores of 133 patients in different active stages of RA were measured and evaluated by using color Doppler ultrasonography.Then,its relationship with erythrocyte sedimentation rate (ESR),anti-CCP antibody,HAQ,DAS28 and other indicators was analyzed statistically.Results (1) Significant differences could be seen in the US7 scores of the patients with severe active RA,as compared with those of the patients with stable,mild and moderate active RA(7.0 VS 0,7.0 VS 1.0,7.0 VS 2.0,7.0 VS 3.0) (P ＜0.05).Ultrasonographic US7 scores were positively correlated with DAS28 and HAQ.(2) US7 revealed that synovitis gray scale (GS) scores accounted for the highest (63.1％),while synovitis blood flow signal (PD) scores,tenosynovitis GS scores,tenosynovitis PD scores and bone destruction scores accounted for (18.3％),(7.2％),(4.3％) and (6.9％) respectively.The most easily affected site in synovitis was dorsal wrist synovium (82.7％),followed by volar MCP Ⅱ synovium (53.3％).The most easily affected site in tenosynovitis was the dorsal wrist joint (15.8％),followed by the dorsal MCPⅡ (15.7％).In bone destruction,the most easily affected site was ulnar MTPV (33.8％),with radialis MCPⅡ (24.1％) being the second.Conclusions Ultrasonographic US7 scores could effectively reflect the disease activity in RA patients,and it was of good value to those with severe active RA.In US7 scores,the rate of synovitis was significantly higher than those of tenosynovitis and bone destruction,and the most easily affected site was dorsal wrist joint and palmar MCPⅡ.Clinically,more attention should be paid to the changes in these two joints.

Objective To explore the effect of tumor necrosis factor-alpha(TNF-α) blockade therapy on circulating Th17 cell percentage and serum interleukin (IL)-17 level in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Methods Twenty-seven RA and 22 AS patients were recruited, of which 14 cases from both diseases received 40 weeks TNF blockade therapy. Twenty-four healthy blood donors were used as controls. The frequencies of circulating Th17 cells were determined by flowcytometry, and serum IL-17 level were measured by enzyme linked immunosorbent assay(ELISA). Results Significantly higher baseline circulating Th17 cells were observed in active RA and AS patients compared with the healthy controls[RA 1.03%(0.66%,1.78%) vs controls 0.50%(0.43%,0.67%), Z=-3.236, P<0.01; AS(1.16±0.09)%vs controls (0.59 ±0.061)% , t =5.226, P <0.01]. Similarly, serum IL-17 level were significantly elevated in patients with both diseases compared with controls[RA(32.3±2.5) pg/ml vs controls(14.3±2.5) pg/ml, t=5.070, P<0.01; AS 28.98(23.84,36.14) pg/ml vs controls 11.84(5.33,22.12) pg/ml, Z=-4.103, P<0.01]. After TNF-α blockade therapy, serum IL-17 was significantly decreased in both diseases groups[RA △(-13.5± 5.0) pg/ml and AS △(-16.0±1.9) pg/ml]. In contrast, no significant differences were found in the frequencies of circulating Th17 cells[RA △(0.104 5±0.212 6)% and AS △(0.002 5±0.183 8)%]. Conclusion Th17 cells and IL-17 have been implicated in the pathogenesis of RA and AS. TNF-α blockade can partially inhibit the function of Th17 cells. However, it is unable to reduce the frequencies of these cells in the circulation after 40 weeks therapy, which may explain the reasons for the relapse.