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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.
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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.
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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 po-tent 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.
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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.
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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.
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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.
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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.
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Objective To investigate the mechanism of hydrogen therapy for gouty arthritis,and provide new strategy for gout via a diet therapy by building up the crystal arthritis (gout) animal model.Methods Wistar rats (200±20) g were randomly divided into five groups which were consisted of five rats,including:the hydrogen-water model group,the hydrogen-feed model group,the hydrogen-water and hydrogenfeed model group,the control model group,and the blank group.And the first,the second,the third group collectively referred to as the hydrogen group.The rat model of acute gouty arthritis was established via injecting monosodium urate (MSU) in rats' ankles,after 14 days continuous feeding.On the third day after injection,serum samples were collected and analyzed.The swelling feet were removed and kept in the 40％ neutral formaldehyde for histochemicalstudies.During the three days after MSU injection,the volume of whole feet (including the ankle joint) was also recorded.The results were analyzed with one-way ANOVA and tamhane's T2 methods.Results In this study,a moderate elevated level of observed parameters,such as swelling joints numbers and inflammatory factor levels,was observed in the hydrogen feed model group than other groups.To measure the volume of rats' feet and found that the volume of feet of the control model group was 1.24 times (0.40±0.06,P＜0.05) as big as hydrogen group.And the TNF-α,IL-1,malondialdehyde in the serum of the hydrogen group were also less than those of the control model group.The contention of TNF-α of the control model group was 6.23 times (336±60,P＜0.05) as much as the hydrogen group.The contention of IL-1β of the control model group was 4.02 times (249±42,P＜0.05) as much as the hydrogen group.The contention of MDA of the control model group was 2.18 times (24±4,P＜0.05) as much as the hydrogen group.Conclusion The oral hydrogen intake has a definite therapeutic effect on controlling articular inflammation,which is helpful in exploring the dietary therapy for gouty arthritis.
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Objective To evaluate the efficacy and safety of two forms of preparations of dexamethasone palmitate in the treatment of rheumatoid arthritis (RA).Methods A multicenter,double-blind,randomized,parallel-group clinical trial was carried out according to good clinical practice (GCP).A total of 237cases of RA patients with mild to moderate knee swelling were randomly divided into the treatment group (n=118 ) or the control group (n=119) and were treated with two kinds of dexamethasone palmitate 8 mg injection respectively.The primary efficacy endpoints were the circumference of the knee joint at the upper and the lower edge after the intra-articular injection.The secondary efficacy endpoints were joint tenderness index and patients general assessment.The adveme events were recorded.Analysis of covariance,t test or Wilcoxon test,x2 test or Fisher exact test were used for statistical analysis.Results The upper edges of the treatment group and the control group after treatment were (37.2±3.3) cm and (36.4±3.9) cm respectively,and the lower edges of the two groups were (34.4±2.9) cm and (33.9±3.4) cm respectively.They were all significantly smaller than the edges before treatment [(38.1± 3.3) cm and (37.3±4.0) cm of the upper edges,(35.1±3.0)cm and (34.6±3.6) cm of the lower edges respectively ) (P＜0.O1)].After treatment,the joint tenderness index were improved (P＜0.01).A total ratio of great improvement and improvement of patients general assessment of the two group patients were 67.5％ (79/117) and 74.8％ (86/115) respectively.No statistical significant difference was found in all primary and secondary efficacy endpoints between the two groups (P＞0.05).During the clinical trial,the incidence of adverse events related to the treatment of two groups were 4.2％ and 6.8％,without any significant difference (P＞0.05).Conclusion New preparation of dexamethasone palmitate has the same efficacy and safety as the imported producted in the treatment of RA.The circumference of the knee joints at the upper and the lower edge may be used to assess the effects of intra-articular injections.
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Objective To assess the efficacy of intedeukin (IL)-1Ra,a recombinant human IL-1receptor antagonist,plus methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) refractory to MTX therapy.Methods A total of 54 patients with active RA,who had been taking MTX at a stable dosage,were randomized to receive daily subcutaneous injections of IL-1Ra (80 mg) or placebo.The proportion of patients who had a response as assessed by ACR20,ACR50 and ACR70 was analyzed using Chi-square test measures.Baseline variables and DAS28 were analyzed using Student's t-test (parametric) or Wilcoxon's rank sum test (nonparametric) as appropriate.Results After 24 weeks,more patients achieved clinical benefits treated with IL-1Ra plus MTX compared with MTX alone (64％ vs 17％,P=-0.004) as determined by the ACR20 improvement.In the IL-1Ra group,an ACR50 response was observed in 38％ and an ACR70 response in 17％.None of the patients treated with MTX alone achieved ACR50 or ACR 70 improvement.However,9 of 42 (21％) patients in the IL-1Ra group,who showed therapeutic response initially,had secondary drug failure to IL-1Ra therapy thereafter.A significant increase in mean DAS28 from baseline was found in the nonresponders to IL-1Ra,compared with placebo.Conclusion IL-IRa is effective for the treatment of patients with active RA by blocking IL-1.However,the efficacy of IL-1Ra is lost soon in about one-fifth of patients in soite of initial good resoonse.
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Objective To study the serum levels of low molecule weight IgM (LMW IgM) in ankylosing spondylitis (AS) patients and rheumatoid arthritis (RA) patients and to evaluate the relationship of LMW IgM levels with the disease activities. Methods The levels of LMW IgM and pentameric IgM in AS patients, RA patients and healthy controls were measured with ELISA after separated using ultrafiltration assay. Differences in the percentage of LMW IgM between subject groups were analysed using Mann-Whitney U test. Results The percentages of LMW IgM increased dramatically in AS patients and RA patients compared with healthy controls (0.194 ± 0123, 0.061 ±0.026, 0.028 ±0.165 separately). The LMW IgM percentages were not correlated with the disease activities. Conclusion The increase of LMW IgM indicates humoral immune function abnormality in AS patients and RA. However, the mechanism needs further study.
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Objective To determine the sensitivity and specificity of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) in the diagnosis of rheumatoid arthritis. Method A total of 1018healthy donors, 212 patients with rheumatoid arthritis, 435 patients with other connective tissue disease were recruited to this study. Anti-CCP antibodies and IgM-rheumatoid factor (RF) were determined by ELISA according to manufacturer instructions, with a cut-off of 20U. Result The frequency of positive anti-CCP antibodies in patients with rheumatoid arthritis is 48.1% (n = 102 ), higher than healthy donors (2.6%,n = 26) and patients with other connective tissue diseases (3.7%, n = 16). The specificity of anti-CCP antibodies is 97.4%. The titer of anti-CCP antibodies in patients with rheumatoid arthritis (429. 7 U) is much higher than that in healthy donors (29. 3 U ) and patients with other connective tissue diseases (36. 5 U). The frequency of positive IgM-RF in patients with rheumatoid arthritis is 94. 3% whilst only21.5% in healthy donors. The false positivity rate of IgM-RF is higher than anti-CCP antibody. Conclusion Anti-CCP antibodies is a highly specific autoantibody in the diagnosis of rheumatoid arthritis.
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Objective To analyze the levels of T helper(Th)17-related cytokines interleukin(IL)-17,IL-22,IL-23 and IL-27 in plasma of patients with systemic lupus erythematosus(SLE).Methods Plasma IL-17,IL-22,IL-23 and IL-27 levels were measured by enzyme-linked immunosorbent assay in 45SLE patients and 32 healthy controls and their associations with each other,disease activity and clinical features were evaluated.Results Plasma levels of IL-17 and IL-23 were significantly higher in SLE patients than in controls[77.8(25.4～487.6)pg/ml vs 36.4(15.7～338.2)pg/ml;14.7(<7.8～247.5) pg/ml vs <7.8(<7.8～81.7)pg/ml.both P<0.01].with no difference between active and inactive disease.In contrast,IL-22 levels were markedly decreased in SLE patients compared with the controls[77.4(<15.6～559.7)pg/ml vs 378.8(21.8～1154.2)pg/ml,P<0.01]and were lower in active disease than in inactive disease(P<0.01).IL-27 levels tended to be higher in SLE patients compared with controls,but the difference was not significant (P>0.05).A strong and positive correlation was found between IL-17 and IL-23 levels(P<0.01)in SLE patients.IL-22 levels were negatively correlated with SLEDAI score,erythrocyte sedimentation rate and antidsDNA antibody titers(all P<0.01),and positively correlated with C3 levels (P<0.05).Each cytokine levels were not related to specific manifestations and treatments.Conclusion Th17 cytokine response in peripheral blood of patients with SLE is abnormal.and IL-17 and IL-22 appear to play different roles in SLE pathophysiology.IL-23/IL-27 imbalance may contribute to the development of Th17-mediated inflammation in SLE.
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OBJECTIVE: Previous opinions consider the secondary diffuse osteoporosis as the very cause of vertebral fractures in patients with ankylosing spondylitis (AS). However, recent studies on bone mineral density (BMD) and vertebral fractures in AS patients reveal that there is no relation between the two. This article aims at investigating the association of lumbar vertebral fractures with clinical, laboratory, and imaging indexes in AS patients.METHODS: A contrast observation was performed between 65 AS patients and 62 healthy physical examinees, whose lumbar vertebral plain radiographs were taken for checking vertebral fractures. Disease activity evaluation indexes included C-reactive protein, erythrocyte sedimentation rate, finger-to-ground distance, Schobar's index score, Bath AS radiology index (BASRI) and syndesmophyte score. Dual energy X-ray absorptiometry technique was used to measure BMD levels of lumbar vertebras and femurs.RESULTS: Out of the total 65 AS patients, 10 ones (15.4%) had lumbar vertebral fractures, with 4 ones with wedge deformities and the other 6 ones with biconcave deformities. BMD levels of Lumbar vertebras and femurs in AS patients were significantly lower than those in controls (P < 0.01). There were significant differences in Schober's index scores, finger-to-ground distance scores, Bath scores, syndesmophyta scores and intertrochanter BMD values between AS patients with and without vertebral fractures (P < 0.01 ). Multiple logistic regression analyses revealed that intertrochanter BMD values were independently associated with lumbar vertebral fractures in AS patients (P =0.043).CONCLUSION: There is a correlation between low femoral BMD levels and the risk of lumbar vertebral fractures in patients with AS, especially at the intertrochanter area.
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Objective To examine the suscepribility of the single nucleotide polymorphisms(SNPs)in IL-1 gene in Chinese Han population to ankylosing spondylitis (AS). Methods An correlation analysis was performed in a case-control cohort of 162 AS cases, 58 patients with other autoimmune diseases and 162 controls. Four SNPs located in the IL-1 gene (rs16944, rs3811058, rs419598, rs315952) were examined by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP). Results The frequencies of allele C at position rs16944, rs3811058, rs419598 significantly increased in AS cases VS controls, so did their genotype frequencies (50% vs 36.3%, 57.9% vs 52.8%, 45.7% vs 12.3%, P＜0.05). The SNPs of these sites significantly influenced the prevalence of AS. Conclusion We discover that SNPs of IL-1 gene Rs16944, Rs419598, Rs3811058 is closely related to the occurrence of AS.
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Objective To characterize and quantify the CD4 +CD25 + regulatory T (Treg) cell population in peripheral blood of patients with ankylosing spondylitis (AS) and to determine the influence of treatment with tumor necrosis factor (TNF)-a inhibitors on them.Methods Peripheral blood mononuclear cells (PBMC) were isolated from 25 patients with active AS,in which 10 patients were treated with 12 weeks of etanercept,and 21 healthy subjects.CD4+CD25high T cells were analyzed using flow cytometry,and mRNA expression of FOXP3 was determined by real-time polymerase chain reaction (PCR).Proliferation of T cells to PHA was measured by WST-1 assay using depleted CD25+ cells by immunomagnetic sorting.Results There was no significant difference in the percentage of CD4+CD25high cells in peripheral blood between patients with active AS and controls (P＞0.05).However,PBMC from patients with active AS expressed reduced levels of FOXP3 mRNA (P＜0.01) which were inversely correlated with C-reactive protein (CRP)(P＜0.01).CD4+CD25+ cells in peripheral blood of both active AS patients and controls exhibited suppressive capacity on the proliferation of effector T cells in vitro (both P＜0.01).Treatment with etanereept increased significantly CD4+CD25high cells and FOXP3 mRNA expression (both P＜0.01),with negative correlations between these increases and decrease in CRP levels (P＜0.05 and P＜0.01,respectively).Conclusion In AS patients,peripheral FOXP3-expressing CD4 +CD25 + Treg cells are abnormal,and are up-regulated by etanercept treatment.This suggests a possible pathogenesis of AS and a potential mechanism for clinical efficacy of TNF-α inhibitors.
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Objective:To investigate the possible role of chemokines monocyte chemoattractant protein-1(MCP-1) and macrophage inhibitory protein-1(MIP-1?) in pathogenesis of rheumatoid arthritis(RA).Methods: Enzyme linked immunosorbent assay(ELISA) was used to determine the serum expression of MCP-1 and MIP-1? in 17 patients with early active RA,18 with advanced active RA,and 15 healthy controls(all aged 18-79 years).Clinical activity indices such as the strength of grip,joint pain index,and joint swelling index were assessed in all subjects;and the serological indices such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),and rheumatoid factors were also determined.The relationships between serum levels of MCP-1, MIP-1? with the clinical activity indices and serological indices were analyzed.Results: The serum levels of MCP-1 in patients with early and advanced RA were higher than that in the controls(P