Yin Su

Peking University, Peping, Beijing, China

Are you Yin Su?

Claim your profile

Publications (33)82.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (≤1 year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(-)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8 % (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(-)]. The scores of synovitis in RA-87(-) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0-25.0) vs. 14.0 (IQR, 10.0-25.0), p > 0.05]. Compared with those in non-RA, RA-87(-) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0-25.0) vs. 6.0 (IQR, 2.0-14.5), p = 0.046; occurrence of PIP synovitis: 53.5 vs. 27.3 %, p = 0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(-) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(-) [OR, 3.1 (95 %CI 1.2-8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria.
    No preview · Article · Jan 2016 · Clinical Rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Synovial fibroblast hyperplasia, T-cell hyperactivity, B-cell overactivation, and the self-perpetuating interactions among these cell types are major characteristics of rheumatoid arthritis (RA). The inflamed joints of RA patients are hypoxic, with upregulated expression of hypoxia-inducible factor-1α (HIF-1α) in RA synovial fibroblasts (RASFs). It remains unknown whether HIF-1α regulates interactions between RASFs and T cells and B cells. We report here that HIF-1α promotes the expression of inflammatory cytokines IL-6, IL-8, TNF-α and IL-1β, and cell-cell contact mediators IL-15, vascular cell adhesion molecule (VCAM)-1, thrombospondin (TSP)-1 and stromal cell-derived factor (SDF)-1 in RASFs. Furthermore, HIF-1α perpetuates RASF-mediated inflammatory Th1- and Th17-cell expansion while differentially inhibiting regulatory B10 and innate-like B cells, leading to increased IFN-γ, IL-17, and IgG production and decreased protective natural IgM secretion. Our findings suggest that HIF-1α perpetuates the interactions between RASFs and T cells and B cells to induce inflammatory cytokine and autoantibody production, thus exacerbating the severity of RA. Targeting HIF-1α may provide new therapeutic strategies for overcoming this persistent disease. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · European Journal of Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate whether the cyclic AMP-responsive element modulator α ( CREMα ) polymorphisms are novel susceptibility factors for systemic lupus erythematosus (SLE), four tag SNPs, rs1057108, rs2295415, rs11592925, and rs1148247, were genotyped in 889 SLE cases and 825 healthy controls. Association analyses were performed on whole dataset or clinical/serologic subsets. Association statistics were calculated by age and sex adjusted logistic regression. The G allele frequencies of rs2295415 and rs1057108 were increased in SLE patients, compared with healthy controls (rs2295415: 21.2% versus 17.8%, OR 1.244, P = 0.019 ; rs1057108: 30.8% versus 27.7%, OR 1.165, P = 0.049 ). The haplotype constituted by the two risk alleles “G-G” from rs1057108 and rs2295415 displayed strong association with SLE susceptibility (OR 1.454, P = 0.00056 ). Following stratification by clinical/serologic features, a suggestive association was observed between rs2295415 and anti-Sm antibodies-positive SLE (OR 1.382, P = 0.044 ). Interestingly, a potential protective effect of rs2295415 was observed for SLE patients with renal disorder (OR 0.745, P = 0.032 ). Our data provide first evidence that CREMα SNPs rs2295415 and rs1057108 maybe novel genetic susceptibility factors for SLE. SNP rs2295415 appears to confer higher risk to develop anti-Sm antibodies-positive SLE and may play a protective role against lupus nephritis.
    Preview · Article · Nov 2015 · Journal of Immunology Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1 %, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.
    Preview · Article · Nov 2015 · Clinical Rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cell immunoreceptor (DCIR) has previously shown an association with rheumatoid arthritis (RA) in Caucasians and Han Chinese. This study was aimed to further investigate whether DCIR polymorphisms are novel susceptibility factors for other autoimmune diseases, i.e. systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS). A total of 1502 patients with SLE, 476 patients with primary SS, and 1278 non-related healthy controls were enrolled in the study. The single-nucleotide polymorphisms (SNPs) rs2377422 and rs10840759 were genotyped using TaqMan assay. The differences in allelic and genotypic distribution between two groups were assessed using Pearson chi-square test, and logistic regression adjusting for age and sex, respectively. P-value <0.025 was considered statistically significant by Bonferroni correction. The SNP rs2377422 confers an increased susceptibility risk to both SLE (allele model: P=7.65×10(-4), OR 1.20; genotype recessive model: P=0.012, OR 1.29), and primary SS (allele model: P=3.74×10(-4), OR 1.31; genotype dominant model: P=1.62×10(-4), OR 2.02). There is no association between rs10840759 and SLE or primary SS. In conclusion, DCIR SNP rs2377422 is a novel genetic susceptibility factor for both SLE and primary SS.
    No preview · Article · Sep 2015 · Human immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12weeks. The efficacy and liver abnormalities were observed. The incidence of abnormal liver function within 12weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Aug 2015 · International immunopharmacology
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimThe aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity.Methods The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data.ResultsA total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 ± 0.69 in LEF 50 group and 4.52 ± 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 ± 1.10 and 3.02 ± 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study.ConclusionA weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis.
    No preview · Article · Aug 2015 · International Journal of Rheumatic Diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Mar 2015 · Rheumatology (Oxford, England)
  • [Show abstract] [Hide abstract]
    ABSTRACT: To summarize the clinical features and laboratory data of 77 patients with hemophagocytic syndrome (HPS). A total of 77 patients of HPS were continuously collected from 2007 to 2014 at our hospital. Their underlying diseases, clinical features, laboratory data, therapy and prognosis were analyzed. Their The patients aged from 3 months to 85 years. The gender ratio was roughly equal. Primary HPS was diagnosed in only 5 cases by gene detection Another 72 cases belonged to secondary HPS. The causes were infection (n = 28), hematologic neoplasm (n = 25), autoimmune diseases (AID, n = 11) and unknown (n = 8). HPS was the initial symptom in nearly half cases of hematologic neoplasm and AID. HPS was characterized by high fever (100%), hypersplenomegaly (81.8%) and lymphadenopathy (40.3%). Laboratory data showed cytopenia (94.8%), serum ferritin elevation (93.2%), hypofibrinogenemia (61.8%), hemophagocytosis in bone marrow (78.1%) and hypertriglyceridemia (55.3%). Low NK-cell activity (95.2%) and elevation of sCD25 (100%) were specific manifestations in HPS. Pulmonary infection (36.4%) and hepatic malfunction (33.3%) were common. Approximately 70% were treated with HLH-2004. Pulse-dose corticosteroid therapy (methylprdnisolone 200-500 mg/d) was used in 8 AID patients. And 14 patients died and 10 withdrew treatment because of exacerbation. Five had complications of DIC and another 5 progressed into MODS. Neoplasm (52.0%) had the highest mortality in secondary HPS. And infection (25.0%) and AID (18.2%) followed. Sometimes HPS occurs simultaneously with autoimmune disease or neoplasm. Relevant laboratory tests for suspected patients may aid an early diagnosis. Presence of DIC or MODS in HPS is possibly correlated with a poor prognosis and a high mortality.
    No preview · Article · Mar 2015 · Zhonghua yi xue za zhi
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6 % (DAS28), 8.4 % (SDAI), 8.2 % (CDAI), and 6.8 % (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.
    No preview · Article · Nov 2014 · Clinical Rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To develop classification criteria for early rheumatoid arthritis (ERA) based on a large cohort of early inflammatory arthritis patients and to evaluate the performance of these criteria. Methods: The study population comprised a cohort of early inflammatory arthritis patients with symptom duration less than one year. Classification criteria of ERA were developed by incorporating the most sensitive or specific variables. Performance of the ERA criteria, 1987 ACR and 2010 ACR/EULAR criteria were evaluated. Results: A total of 803 patients were enrolled in this study. By the end of the one year follow-up, 514 patients were diagnosed with RA, 251 with other rheumatic diseases, and 38 patients with undifferentiated arthritis. The ERA criteria are as follows: 1) morning stiffness ≥30 minutes; 2) arthritis of 3 or more joint areas; 3) arthritis of hand joints; 4) positive RF; 5) positive anti-CCP antibody. Rheumatoid arthritis is defined by the presence of 3 or more of the criteria. The sensitivity (84.4%) of the ERA classification criteria was much higher than the 1987 ACR criteria (58.0%). In a validation cohort of early inflammatory arthritis patients, the area under the ROC curves (AUC) showed a better performance for the ERA criteria (0.906, 95%CI 0.866 to 0.945) than the 1987 ACR criteria (0.786, 95%CI 0.725 to 0.848) and the 2010 ACR/EULAR criteria (0.745, 95%CI 0.677 to 0.814). Conclusions: A set of ERA classification criteria has been developed with good performance for early RA. It is applicable in clinical practice and research.
    No preview · Article · Sep 2014 · Clinical and experimental rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. Objectives To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases—for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Methods The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3 expression was evaluated. Results The functional LILRA3 conferred high susceptibility to both SLE (p=3.51×10−7, OR=2.03) and pSS (p=1.40×10−3, OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10−7, OR=2.19) and thrombocytopenia (p=1.68×10−5, OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39×10−4, OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10−3, OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10−8) and pSS (p=1.49×10−7) than in controls. Conclusions Functional LILRA3 is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To estimate the annual direct and indirect costs of rheumatoid arthritis (RA) in China and identify the predictors for cost of illness. MethodsA cross-sectional study of cost of illness from the societal perspective was conducted on 829 patients with RA in 21 tertiary care hospitals in China between July 2009 and December 2010. 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. ResultsThe mean SD total cost of RA in China was $3,826 +/- $5,659 per patient-year, given a gross domestic product 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 the total costs, dominated by biologic agents (48.2%) and disease-modifying antirheumatic drugs (23.5%). Additionally, the cost of extracted herbal drugs and traditional Chinese medicine comprised approximate to 17.6% of the drug expense. Higher education level, noninsured status, longer disease duration, more extraarticular manifestations, and higher Health Assessment Questionnaire 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.
    Full-text · Article · Apr 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective . To investigate the expression and clinical significance of trans-membrane MerTK (mMer) on circulating CD14+ monocytes/macrophages and soluble MerTK (sMer) levels in plasma in systemic lupus erythematosus (SLE). Method . 108 SLE patients and 42 healthy controls were recruited in this study. The expression of mMer on the surfaces of CD14+ monocytes/macrophages was evaluated by flow cytometry (FCM). The sMer levels were measured by ELISA. Real-time quantitative PCR was applied to evaluate the mRNA levels of MerTK and ADAM17. Results . Both mMer expression on CD14+ monocytes/macrophages and sMer levels in plasma significantly increased in SLE patients compared to healthy subjects. The frequency of anti-inflammatory MerTK expressing CD14+CD16+ monocytes decreased in SLE. mMer expression was positively correlated with CD163 expression on CD14+ cells. Both the mMer expression on CD14+ monocytes/macrophages and sMer levels in plasma were positively correlated with SLEDAI. Furthermore, more elevated mMer and sMer levels were found in patients with higher SLEDAI, presence of anti-SSA, anti-Sm autoantibodies, and lupus nephritis. Conclusion . Both mMer and sMer levels significantly increased in SLE and positively correlated with disease activity and severity. The upregulation of MerTK expression may serve as a biomarker of the disease activity and severity of SLE.
    Full-text · Article · Mar 2014 · Journal of Immunology Research
  • Jing Liu · Yuan Jia · Ru Li · Yin Su
    [Show abstract] [Hide abstract]
    ABSTRACT: To understand the clinical profiles of coexisting rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Coexisting RA and AS was discussed with 3 cases, 108 similar cases were found in the literature and reviewed here. Coexisting RA and AS was rarely reported. The patients might have family histories of its related diseases, and initially present with diverse symptoms mainly in their youth. All the patients displayed severe symmetrical axial and peripheral arthritis. Joint destruction observed by imaging and the loss of functions were obvious. The prevalence of autoantibodies and HLA alleles was low. Most of the patients hardly demonstrated a good response to ordinary therapies. Patients with coexisting RA and AS present with various symptoms initially and have considerable joint dysfunction as well as unfavorable outcomes. They should receive aggressive therapeutic strategies.
    No preview · Article · Feb 2014 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · May 2013 · Annals of the rheumatic diseases
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several studies have reported STAT4 polymorphism is strongly associated with increased susceptibility to rheumatoid arthritis (RA). However, a study from China showed no association between STAT4 and RA susceptibility in a Chinese Han subpopulation. Since the northern Hans are known to be genetically different from the southern Hans, the aim of this study was to investigate the association of STAT4 polymorphism with RA in a large cohort of a northern Chinese Han subpopulation. 640 RA patients and 662 healthy controls were enrolled. DNA samples were genotyped for STAT4 rs7574865 by direct sequencing. The association of single nucleotide polymorphism (SNP) rs7574865 with RA susceptibility was calculated and the relationship between rs7574865 polymorphism and RA subgroups stratified by clinical features was estimated. We confirmed a significant association of STAT4 rs7574865 polymorphism with RA susceptibility in northern Chinese Han population. The frequency of the minor T allele in RA was significantly higher than in healthy controls (35.2% vs. 31.1%; P = 0.029, OR 1.2 [95% CI 1.02-1.41]). There was also a significant difference in the distribution of the genotypes of SNP rs7574865 between RA patients and healthy controls (P = 0.02). Stratification analyses showed no associations between the genetic risk and clinical/serologic features, but a potential high frequency of TT genotype in a rheumatoid factor-negative subgroup, although it did not reach statistical significance (P = 0.084, OR 2.01 [95% CI 0.91-4.45]). STAT4 rs7574865 is significantly associated with RA susceptibility in northern Chinese Han subpopulations. The genetic differences of Han subpopulations should be considered when genetic susceptibility for diseases is studied.
    No preview · Article · Apr 2013 · International Journal of Rheumatic Diseases
  • Source
    Yun-Yan Zhu · Yin Su · Zhan-Guo Li · Yu Zhang
    [Show abstract] [Hide abstract]
    ABSTRACT: Altered Toll-like receptor (TLR) signaling has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The present study was undertaken to characterize responses of B cells from SLE patients to TLR7 and TLR9 stimulation and to explore the potential role of single immunoglobulin interleukin-1 receptor related molecule (SIGIRR) in the regulation of TLR-mediated responses of SLE B cells. Peripheral blood mononuclear cells (PBMC) were isolated from 64 patients with SLE and 37 healthy donors. CD19+ B cells purified using microbeads were cultured with TLR7 or TLR9 agonists. Cell proliferation was measured by thymine incorporation and the frequency of antibody-secreting cells was determined by ELISPOT assay. SIGIRR expression in PBMCs and B cells was analyzed using flow cytometry analysis. In contrast to the enhanced proliferation following B cell receptor (BCR) engagement, B cells from SLE patients exhibited a virtually normal proliferative response to TLR7 or TLR9 stimulation. Moreover, B cells from SLE patients and healthy donors were almost equally competent to differentiate into antibody-secreting cells upon TLR engagement except for a reduction in the generation of IgG-secreting cells by TLR9-stimulated lupus B cells. In line with these somehow unexpected observations, SLE B cells were found to express a significantly higher level of SIGIRR than normal B cells. Despite the reported upregulation of TLR7 and TLR9 expression in B cell from SLE patients, their responses to TLR stimulation were largely normal. The increased expression of the negative regulator SIGIRR may be partly responsible for the "balance of terror".
    Full-text · Article · Aug 2012 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Aug 2012 · Chinese medical journal
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Apr 2012 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences