Rong Mu

Peking University, Peping, Beijing, China

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Publications (24)65.17 Total impact

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    ABSTRACT: Aims: This study was designed to investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese compared with Europeans. Methods: A genome-wide association study was conducted in China with 952 cases and 943 controls and 32 variants were followed up in 2132 cases and 2553 controls. A trans-population meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the two ethnic remote populations Results: Three non-MHC loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated peptide antibody (ACPA) positive cases than those in ACPA-negative cases. These include two novel variants, rs12617656 located in an intron of DPP4 (odds ratio (OR) = 1.56, P = 1.6 × 10(-21) ) and rs12379034 located in the coding region of CDK5RAP2 (OR = 1.49, P = 1.1 × 10(-16) ), as well as a variant at the known CCR6 locus (rs1854853, OR = 0.71, P = 6.5 × 10(-15) ). The analysis of ACPA-positive cases vs. ACPA-negative cases revealed that rs12617656 at the DDP4 locus showed a strong interaction effect with ACPA (P = 5.3 × 10(-18) ) and such an interaction was also observed at the MHC locus (rs7748270, P = 5.9 × 10(-8) ). The trans-population meta-analysis showed genome-wide overlap and enrichment in association signals across the two populations, confirmed by prediction analysis. Conclusions: This study has expanded the risk alleles list of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 01/2014; · 7.48 Impact Factor
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    ABSTRACT: To explore the prevalence and characteristics of main organ involvement in adult patients with polymyositis (PM) or dermatomyositis (DM) and determine their specific relative factors. Using unified questionnaire, we retrospectively collected the medical records of 1 387 confirmed adult PM/DM patients from 2007 to 2012 at 22 rheumatology centers in China. Statistical analyses were performed with chi-square or Fisher exact test and multivariate analyses with logistic regression. A total of 1 387 patients were collected with 460 (33.2%) PM and 927 (66.8%) DM. The female:male ratio was 2.4: 1. Their onset age was ( 47 ± 14) years. A total of 1 031 (74.3%) patients had organ involvement. The prevalence of pulmonary involvement, arthritis, gastrointestinal and cardiac involvement were 44.6%, 32.3%, 21.9% and 20.3% respectively. The multivariate analysis indicated that older onset age (P < 0.01) was positively associated with pulmonary involvement while myalgia (P < 0.05) was negatively associated. Fever (P < 0.05), weight loss (P < 0.05) and Raynaud's phenomenon (P < 0.01) were positively associated with arthritis while muscle weakness (P < 0.05) negatively associated. Weight loss (P < 0.05), Raynaud's phenomenon (P < 0.01) and muscle weakness (P < 0.05) were positively associated with gastrointestinal involvement. Weight loss (P < 0.05) and swollen limbs (P < 0.05) were positively associated with cardiac involvement. The prevalence of organ involvement is high in adult PM/DM patients. Our study may aid the diagnosis of organ damage in PM/DM patients.
    Zhonghua yi xue za zhi 01/2014; 94(1):43-6.
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    ABSTRACT: Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin-33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL-33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development.
    Immunology 01/2014; 141(1). · 3.71 Impact Factor
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    ABSTRACT: This study aims to investigate the incidence of hepatitis B virus (HBV) reactivation in inflammatory arthritis (IA) patients with HBV infection using anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral therapy in reducing the risk of viral reactivation in chronic HBV infection. IA patients using anti-TNF agents from six centers were enrolled. Their HBV infection conditions and ALT and HBV-DNA levels were monitored periodically. Among the six chronic hepatitis B patients, HBV reactivation was found in two patients without antivirus prophylaxis and no viral replication was detected in the other four patients with antivirus prophylaxis. In the 31 inactive carriers, the increase of viral load was detected in 6 of 22 (27.3 %) patients without antiviral prophylaxis, and there was no viral reactivation in the other 9 patients with antiviral prophylaxis. HBV reactivation was not found in the 50 patients with resolved HBV infection. It is suggested that anti-TNF therapy might increase the risk of HBV reactivation in patients with chronic HBV infection, and antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem to be safe in patients with resolved HBV infection.
    Clinical Rheumatology 09/2013; · 2.04 Impact Factor
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    ABSTRACT: Objective: To estimate the annual direct and indirect costs of rheumatoid arthritis (RA) in China, and identify the predictors for cost-of-illness. Methods: A cross-sectional study of cost-of-illness was conducted on 829 patients with RA in 21 tertiary care hospitals in China between July 2009 and December 2010 from the societal perspective. Data on demographics, clinical variables, and components of costs were collected by physician interview. Costs were represented in 2009 US dollars ($) using purchasing power parity estimates. Univariate and multivariate linear regression analyses were performed to identify the predictors for cost-of-illness. Results: The mean (S.D.) total costs of RA were $3,826 (5,659) per patient-year in China, given GDP per capita of $6,798 in China in 2009. Direct costs and indirect costs comprised 90.0% and 10.0% of the total costs, respectively. Drug expense represented approximately half of total costs, dominated by biologics (48.2%) and DMARDs (23.6%). Besides, the costs of extracted herbal drugs and traditional Chinese medicine were about 17.6% of drug expense. Higher education level, non-insured status, longer disease duration, more extra-articular manifestations, and higher HAQ score independently predicted higher total costs. Conclusion: Our results provide the first study of costs of RA in China. This study not only demonstrates the economic burden of RA, but also identifies the predictors that could be interventional factors to reduce the societal costs of RA in China. © 2013 American College of Rheumatology.
    Arthritis care & research. 09/2013;
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    ABSTRACT: Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain and fatigue. It is a less frequently diagnosed disease in China, thus Chinese rheumatologists may have lower awareness of FM compared with colleagues in Western countries. The aim of this study is to investigate the perceptions of FM in Chinese rheumatologists and analyze their therapeutic approach in clinical practice. An anonymous questionnaire survey was conducted among a nationwide sample of Chinese rheumatologists at the 15th National Rheumatology Conference in 2010. The 20-question survey included questions regarding background, work experience, perceptions of diagnosis and behaviors of treatment related to FM. Continuing medical education (CME) information was also collected in the survey. Seven hundred and seven rheumatologists responded to the questionnaire, a response rate of 60%. Less than one-fifth of the respondents were experienced in dealing with FM. Although most of the respondents regarded FM as a distinct pathological entity, nearly 30% of Chinese rheumatologists believed that FM was only a psychological disorder. The respondents recognized some of the FM-related symptoms, but had limited knowledge on the diagnostic criteria. Eighty percent of the respondents declared they had difficulties in treating FM patients. However, nearly all (90.8%) respondents believed that the prognosis of FM patients was usually benign. Our data also showed that most Chinese rheumatologists were eager for CME on FM. The awareness and perception of FM are still low among Chinese rheumatologists. CME on FM is needed for improving the quality of health care in China.
    International Journal of Rheumatic Diseases 06/2013; 16(3):258-63. · 1.65 Impact Factor
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    ABSTRACT: OBJECTIVES: Hyperplasia of synovial fibroblasts, infiltration with lymphocytes and tissue hypoxia are major characteristics of rheumatoid arthritis (RA). Extensive data support a key role for toll-like receptors (TLRs) in RA. Little is known regarding the impact of hypoxia on TLR-induced inflammation in RA. The aim of this study was to reveal the effects of hypoxia and its regulator, hypoxia-inducible factor-1α (HIF-1α), on the inflammatory response of RA synovial fibroblasts (RASF) to TLR ligands. METHODS: Hypoxia was induced in RASF by incubation with Na2S2O4. TLR3 ligand polyIC, TLR2 ligand peptidoglycan, TLR4 ligand LPS and TLR9 ligand CpG were used to stimulate the cells. Effects of hypoxia on TLR-induced inflammatory mediators were determined by RT-PCR, qPCR and ELISA. Overexpression of HIF-1α as well as knocking-down its expression was used to reveal its fundamental role. RASF-induced inflammatory T cell expansion was determined by flow cytometry analysis of T helper (Th)1/Th17 cells, and IFN-γ/IL-17 production by ELISA after RASF/T cell coculture. RESULTS: Hypoxia potentiated the expression of inflammatory cytokines, metalloproteinases and VEGF in RASF stimulated by different TLR ligands, especially polyIC, a synthetic mimic of dsRNA from viruses or apoptotic cells. HIF-1α played a fundamental role in this synergy. Moreover, HIF-1α overexpression enhanced RASF-mediated expansion of inflammatory Th1 and Th17 cells, leading to proinflammatory IFN-γ and IL-17 production. CONCLUSIONS: Our findings suggest that hypoxia and HIF-1α may function in conjunction with TLR-stimulated innate immune responses to drive inflammation in RA. This pathway may serve as a therapeutic target for the disease.
    Annals of the rheumatic diseases 05/2013; · 8.11 Impact Factor
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    ABSTRACT: OBJECTIVE.: To investigate the reason why the level of LYN is significantly decreased in B cell from a majority of patients with systemic lupus erythematosus (SLE) and to determine the role of microRNA-30a (miR-30a) in B cell hyperactivity of patients with SLE. METHODS.: Luciferase reporter gene assays were performed to identify the interaction between miR-30a and three prime untranslated region (3'UTR) of LYN. The level of miR-30a in B cell was determined by TaqMan quantitative polymerase chain reaction (qPCR) analysis. LYN messenger RNA level was tested by real-time qPCR. The protein level of LYN was determined by Western blotting. The quantity of IgG was determined by enzyme-linked immunosorbent assay. The proliferation of B cell was measured by [3 H]-thymidine incorporation. RESULTS.: We demonstrated that miR-30a, but not miR-30b/c/d/e, could specifically bind the 3'UTR of LYN in B cell lines. Meanwhile, overexpression of miR-30a could inhibit the level of LYN. The level of miR-30a was significantly higher in B cell from SLE patients than that in B cell from health donor. The level of miR-30a was negatively associated with the level of LYN in B cell. Overexpression of miR-30a could promote the proliferation of B cell lines and the production of IgG antibodies. The effect of miR-30a could be recovered by overexpression of LYN in B cell. CONCLUSION.: We herein reveal that the elevated miR-30a is responsible for the reduction of LYN in B cell from the patients of SLE and consequently plays an important role in B cell hyperactivity. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 02/2013; · 7.48 Impact Factor
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    ABSTRACT: Objectives. IL-33, a newly found cytokine which is involved in joint inflammation, could be blocked by a decoy receptor-sST2. The expression and correlation of IL-33 and sST2 in rheumatoid arthritis (RA) are of great interest. Methods. Synovial fluid (SF) was obtained from 120 RA and 30 osteoarthritis (OA) patients, and paired sera were collected from 54 of these RA patients. The levels of IL-33 and sST2 were measured by ELISA. Results. SF IL-33 was significantly higher in RA than in OA, which was correlated with disease activity score 28, erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose phosphate isomerase (GPI), and immunoglobulin. Serum IL-33 was correlated positively with SF IL-33 in RA. Furthermore, it was correlated with RF-IgM and GPI. sST2 was partly detectable in RA (13 out of 54, 24.1%), while not in OA. Serum sST2 in RA had no significant correlation with serum IL-33 or SF IL-33. However, SFs from both RA and OA patients did not express sST2. Conclusions. This study supported that IL-33 played an important role in the local pathogenesis of RA. Considering the tight correlation between IL-33 and clinical features, it may become a new target of local treatment.
    Clinical and Developmental Immunology 01/2013; 2013:985301. · 3.06 Impact Factor
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    ABSTRACT: Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1α (HIF-1α) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1α and IL-33 in the synovial fibroblasts. Knocking down HIF-1α compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1α expression in RASF substantially upregulated IL-33 levels. HIF-1α promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1α expression in RASF, thus forming a HIF-1α/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1α may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.
    PLoS ONE 01/2013; 8(8):e72650. · 3.73 Impact Factor
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    ABSTRACT: Toll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE. mRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA). TLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients. TLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.
    Chinese medical journal 08/2012; 125(16):2873-7. · 0.90 Impact Factor
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    ABSTRACT: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.
    Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2012; 44(2):182-7.
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    ABSTRACT: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.
    Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2012; 44(2):176-81.
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    ABSTRACT: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.
    Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2012; 44(2):188-94.
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    ABSTRACT: To investigate the prevalence of eight common rheumatic diseases in a large Chinese population. A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature. A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%). This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.
    Rheumatology (Oxford, England) 12/2011; 51(4):721-9. · 4.24 Impact Factor
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    ABSTRACT: To investigate the clinical significance of D-dimer in systemic lupus erythematosus (SLE). The study group comprised 261 SLE patients who were admitted in ward from 2005 to 2008 in Peking University People's Hospital. Collect the clinical data to investigate the clinical significance of D-dimer. (1) The D-dimer levels of 56 patients were increased due to coexist reduced renal function, infections, disseminated intravascular coagulation (DIC), liver disorders, pregnancy and injury. With the exception of above patients, 142 (69.3%) patients were increased in total 205 patients. (2) The level of D-dimer was positively correlated with SLE disease activity index (SLEDAI) score (r = 0.598, P = 0.000), and was associated with anti-dsDNA antibody, ESR, C-reactive protein (CRP) and complement C(3) and C(4). (3) D-dimer level was associated with important organ involvement. (4) All patients with thrombosis had increased D-dimer, but patients without thrombosis had normal or increased D-dimer levels. The level of D-dimer elevates in patients with active disease or important organ involvement, it can not identify thrombosis. All patients with thrombosis had increased D-dimer levels.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 12/2010; 49(12):1039-42.
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    ABSTRACT: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated. The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored. In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-β1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-β1 and NO and UC-MSCs could promote the expansion of CD4(+) Foxp3(+) regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-α, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA. In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.
    Arthritis research & therapy 11/2010; 12(6):R210. · 4.27 Impact Factor
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    ABSTRACT: Interleukin 33 (IL-33) is a novel cytokine involved in joint inflammation in animal models. We analyzed the expression of IL-33 in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and investigated its possible pathophysiological importance. The concentration of IL-33 was measured by ELISA in the serum of 223 patients with RA and 159 controls. Anticyclic citrullinated peptide, rheumatoid factor (RF)-IgA, and RF-IgG were tested by ELISA. Antikeratin antibody and antiperinuclear factor were tested by indirect immunofluorescence assay. Erythrocyte sedimentation rate, C-reactive protein, and immunoglobulins were measured by standard laboratory techniques. The association of IL-33 level with clinical and serologic features of RA was analyzed. We tested the change of IL-33 level following tumor necrosis factor (TNF-α) blockade therapy in 40 patients with RA. In contrast to almost no detectable IL-33 in osteoarthritis and healthy serum, IL-33 could be detected in 94 out of the 223 RA cases (42.2%). Serum IL-33 concentration was significantly higher in patients with RA than in control groups. The level of serum IL-33 decreased after anti-TNF treatment. The level of serum IL-33 was correlated with the production of IgM and RA-related autoantibodies including RF and anticitrullinated protein antibodies. However, no correlation was found between IL-33 concentration and acute-phase inflammation reactant or the score of the Disease Activity Index, suggesting a complex or indirect character of the link between IL-33 and the inflammation in RA. The level of IL-33 is abnormally elevated in RA serum. The elevation of serum IL-33 was at least partly attributed to excessive TNF-α in RA. IL-33 might be involved in the regulation of autoantibody production in RA.
    The Journal of Rheumatology 10/2010; 37(10):2006-13. · 3.26 Impact Factor
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    ABSTRACT: Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and adaptive immunity. There is therefore intense interest in the factors that integrate these immunologic pathways in rheumatoid arthritis. In this paper, we report that IL-33, a novel member of the IL-1 family, can exacerbate anti-glucose-6-phosphate isomerase autoantibody-induced arthritis (AIA). Mice lacking ST2 (ST2(-/-)), the IL-33 receptor alpha-chain, developed attenuated AIA and reduced expression of articular proinflammatory cytokines. Conversely, treatment of wild-type mice with rIL-33 significantly exacerbated AIA and markedly enhanced proinflammatory cytokine production. However, IL-33 failed to increase the severity of the disease in mast cell-deficient or ST2(-/-) mice. Furthermore, mast cells from wild-type, but not ST2(-/-), mice restored the ability of ST2(-/-) recipients to mount an IL-33-mediated exacerbation of AIA. IL-33 also enhanced autoantibody-mediated mast cell degranulation in vitro and in synovial tissue in vivo. Together these results demonstrate that IL-33 can enhance autoantibody-mediated articular inflammation via promoting mast cell degranulation and proinflammatory cytokine production. Because IL-33 is derived predominantly from synovial fibroblasts, this finding provides a novel mechanism whereby a host tissue-derived cytokine can regulate effector adaptive immune response via enhancing innate cellular activation in inflammatory arthritis.
    The Journal of Immunology 02/2010; 184(5):2620-6. · 5.52 Impact Factor
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    ABSTRACT: IL-33, a cytokine of the IL-1 family, is closely associated with type II T cell responses. Here, we report an unexpected proinflammatory role of IL-33 in inflammatory arthritis. IL-33 was expressed in synovial fibroblasts from patients with rheumatoid arthritis (RA). Expression was markedly elevated in vitro by inflammatory cytokines. Mice lacking ST2, the IL-33 receptor alpha-chain, developed attenuated collagen-induced arthritis (CIA) and reduced ex vivo collagen-specific induction of proinflammatory cytokines (IL-17, TNFalpha, and IFNgamma), and antibody production. Conversely, treatment of wild-type (WT) but not ST2(-/-) mice with IL-33 exacerbated CIA and elevated production of both proinflammatory cytokines and anti-collagen antibodies. Mast cells expressed high levels of ST2 and responded directly to IL-33 to produce a spectrum of inflammatory cytokines and chemokines in vitro. In vivo, IL-33 treatment exacerbated CIA in ST2(-/-) mice engrafted with mast cells from WT but not from ST2(-/-) mice. Disease exacerbation was accompanied by elevated expression levels of proinflammatory cytokines. Our results demonstrate that IL-33 is a critical proinflammatory cytokine for inflammatory joint disease that integrates fibroblast activation with downstream immune activation mainly via an IL-33-driven, mast-cell-dependent pathway. Thus, this IL-1 superfamily member represents a therapeutic target for RA.
    Proceedings of the National Academy of Sciences 09/2008; 105(31):10913-8. · 9.74 Impact Factor

Publication Stats

247 Citations
19 Downloads
2k Views
65.17 Total Impact Points

Institutions

  • 2006–2014
    • Peking University
      Peping, Beijing, China
  • 2013
    • Peking University Health Science Center
      Peping, Beijing, China
  • 2004–2013
    • Peking University People's Hospital
      Peping, Beijing, China