Publications by authors named "Guo Chun Wang"

46 Publications

Clinical characteristics of anti-isoleucyl-tRNA synthetase antibody associated syndrome and comparison with different patient cohorts.

Clin Exp Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objectives: This study aimed to analyse the clinical features of anti-isoleucyl-tRNA synthetase (OJ) antibodies in Chinese patients and to compare with previously published cohorts. We reviewed the clinical data of anti-OJ antibody positive patients, including their long-term follow-up.

Results: Anti-OJ antibodies were present in 10 of 1269 (0.8%) patients with idiopathic inflammatory myopathies (IIMs), and 10/320 (3.1%) patients with anti-synthetase syndrome (ASS). Of the anti-OJ antibody-positive patients, 90% had interstitial lung disease (ILD), of whom three (30%) developed rapidly progressive ILD (RP-ILD). Half (50%) of the patients were febrile and developed myocardial involvement; 40% of patients experienced myositis, mechanic's hands and arthritis. Compared to the anti-Jo-1 group, the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the anti-OJ antibody-positive group were higher (p<0.05). From a review of the literature regarding the clinical features of anti-OJ, fever was more common in the eastern cohort (41.7% vs. 8.3%, p=0.002), whereas patients in western countries were more likely to develop arthritis (20.9% vs. 58.1%, p=0.001). With complete follow-up of the present cohort, 80% improved with treatment, including one patient who underwent lung transplant.

Conclusions: The anti-OJ antibody occurred infrequently in Chinese patients, ILD was the major clinical feature, but myocardial injury was also a prominent associated complication. Anti-OJ positive patients were responsive to treatment.
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June 2021

Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease.

Front Cell Dev Biol 2021 25;9:628128. Epub 2021 Mar 25.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China.

Background: Dermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD.

Methods: A total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated .

Results: Serum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all < 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9-44.7) vs. 16.2 (10.0-26.9) ng/mL, < 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 ± 0.3 ng/mL, = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 ( = 0.659, = 0.020) and IFIH1 ( = 0.787, = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.

Conclusions: Among anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.
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http://dx.doi.org/10.3389/fcell.2021.628128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027128PMC
March 2021

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

Adv Ther 2021 01 25;38(1):772-781. Epub 2020 Nov 25.

Eli Lilly and Company, Shanghai, China.

Introduction: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate.

Methods: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively.

Results: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks.

Conclusions: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE.

Trial Registration: ClinicalTrials.gov identifier, NCT02265705.
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http://dx.doi.org/10.1007/s12325-020-01572-yDOI Listing
January 2021

Increased Levels of Soluble CD206 Associated with Rapidly Progressive Interstitial Lung Disease in Patients with Dermatomyositis.

Mediators Inflamm 2020 26;2020:7948095. Epub 2020 Oct 26.

Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China.

Objective: Soluble CD206 (sCD206) is considered a macrophage activation marker, and a previous study proved it as a potential biomarker to predict the severity of anti-melanoma differentiation-associated gene 5- (anti-MDA-5-) positive dermatomyositis- (DM-) associated interstitial lung disease (ILD). To investigate the role of sCD206 in various subtypes of DM, we evaluated the serum level of sCD206 in patients with different myositis-specific autoantibodies besides anti-MDA-5 and clarified its clinical significance.

Methods: Commercial enzyme-linked immunosorbent assay kits were used to detect serum concentrations of sCD206 in 150 patients with DM and 52 healthy controls (HCs). Correlations between sCD206 levels and clinical features, laboratory examinations, and pulmonary function test parameters were analysed.

Results: The median concentrations of serum sCD206 in DM patients were significantly higher than those in HCs ( < 0.0001). Furthermore, median sCD206 levels were elevated in patients with ILD ( = 0.001), especially in those with rapidly progressive ILD (RP-ILD) ( < 0.0001). In addition, sCD206 levels were negatively correlated with the pulmonary function test results, including the percent predicted forced vital capacity ( = -0.234, = 0.023), percent predicted forced expiratory volume in one second ( = -0.225, = 0.030), and percent predicted carbon monoxide diffusion capacity ( = -0.261, = 0.014). Age- and gender-adjusted multivariable analysis showed that sCD206 was an independent prognostic factor for RP-ILD in patients with DM. A longitudinal study showed that sCD206 levels were positively correlated with the physician global assessment visual analog scale scores ( = 54.201, = 0.001).

Conclusion: Serum sCD206 levels were significantly increased in patients with DM and significantly associated with RP-ILD, suggesting that sCD206 is an important biological predictor of RP-ILD in patients with DM.
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http://dx.doi.org/10.1155/2020/7948095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641712PMC
October 2020

A novel autoantibody targeting calreticulin is associated with cancer in patients with idiopathic inflammatory myopathies.

Clin Transl Immunology 2020 15;9(10):e1195. Epub 2020 Oct 15.

Department of Rheumatology China-Japan Friendship Hospital Beijing 100029 China.

Objectives: To investigate the prevalence and clinical significance of anti-calreticulin autoantibodies (anti-CRT Ab) in a large cohort of idiopathic inflammatory myopathy (IIM) patients.

Methods: Sera from 469 patients with IIM, 196 patients with other connective tissue diseases, 28 patients with solid tumors and 81 healthy controls were screened for anti-CRT Ab by enzyme-linked immunosorbent assay using human recombinant CRT protein. Sera from 35 IIM patients were tested using an immunoprecipitation assay to confirm the presence of anti-CRT Ab. Subsequently, IIM-cancer patients were identified and divided into new-onset, remission and recurrent groups based on their cancer status. The relationships between anti-CRT Ab levels and IIM disease activity were also investigated.

Results: Serum anti-CRT Ab was detected positive in 81 of the 469 (17.3%) IIM patients. Immunoprecipitated bands were observed at a molecular weight of 60 kDa corresponding to the CRT protein. The IIM patients with anti-CRT Ab more frequently had cancers compared to the patients without anti-CRT Ab. Moreover, the prevalence of anti-CRT Ab differed according to the cancer status. The IIM patients with recurrent cancers had a much higher prevalence of anti-CRT Ab than those with cancers in remission. Also, serum anti-CRT Ab levels positively correlated with disease activity at baseline and at follow-up visits.

Conclusion: We report the existence of serum anti-CRT Ab in IIM patients and demonstrate the possible association of anti-CRT Ab with malignancy in IIM patients. Serum anti-CRT Ab could serve as a novel candidate marker of cancer in IIM patients.
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http://dx.doi.org/10.1002/cti2.1195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558046PMC
October 2020

Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgroup Analyses: Results from Study RA-BALANCE.

Rheumatol Ther 2020 Dec 2;7(4):851-866. Epub 2020 Sep 2.

Peking University People's Hospital, Beijing, China.

Introduction: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment.

Methods: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics.

Results: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups.

Conclusions: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period.

Trial Registration: NCT02265705.
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http://dx.doi.org/10.1007/s40744-020-00231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695798PMC
December 2020

Anti-Mi-2 antibodies characterize a distinct clinical subset of dermatomyositis with favourable prognosis.

Eur J Dermatol 2020 Apr 13. Epub 2020 Apr 13.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital. Yinghua East Road, Chaoyang District, Beijing 100029.

Background: Anti-Mi-2 antibody is a type of myositis-specific autoantibody found in idiopathic inflammatory myopathy patients.

Objectives: To investigate the clinical features and long-term outcomes in anti-Mi-2-positive dermatomyositis (DM) patients.

Materials And Methods: Serum anti-Mi-2β antibodies were detected in 357 DM patients by enzyme-linked immunosorbent assays, and possible associated clinical features were investigated based on cross-sectional and longitudinal studies.

Results: Of the DM patients, 40/357 (11.2%) were positive for anti-Mi-2β antibodies and found to have a significantly higher frequency of V sign (72.5% vs 45.7%; p = 0.001), shawl sign (60.0% vs 35.6%; p = 0.003), and muscle weakness (77.5% vs 57.1%; p = 0.013), but a lower incidence of interstitial lung disease (ILD) (37.5% vs 60.9%; p = 0.005) and malignancy (0% vs 12.0%; p = 0.041) than anti-Mi-2β-negative patients. Anti-Mi-2β antibody levels positively correlated with disease activity. After a median follow-up period of 44 months, 97.0% of patients showed clinical remission. Twenty-six anti-Mi-2β-positive patients had a disease course longer than two years, and 16/26 (61.5%) were monocyclic without relapse. Moreover, five patients (15.1%) were drug-free with complete remission for more than three months. Kaplan-Meier survival curves showed that DM patients with positive anti-Mi-2β had a significantly lower mortality rate compared to anti-Mi-2β-negative patients (log-rank; p = 0.035). Interestingly, anti-Mi-2β antibodies did not disappear in all patients over time.

Conclusion: Anti-Mi-2β antibodies were associated with a subgroup of DM with a low frequency of ILD and malignancy, good treatment response, and favourable outcome. Moreover, anti-Mi-2β levels correlated with disease activity.
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http://dx.doi.org/10.1684/ejd.2020.3750DOI Listing
April 2020

Identification of a novel autoantibody against heat shock factor 1 in idiopathic inflammatory myopathy.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1191-1200. Epub 2020 Mar 5.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China.

Objectives: Myositis autoantibodies show great utility in the diagnosis and clinico-serological phenotyping of idiopathic inflammatory myopathy (IIM). We identified a novel autoantibody against heat shock factor 1 (HSF1) and further evaluated its disease specificity and clinical significance in IIM patients.

Methods: A human protein microarray was used to identify autoantibodies in myositis sera. ELISA, immunoblot and dot blot assays were applied to examine anti-HSF1 autoantibodies in IIM patients and controls. Immunofluorescence was used to detect HSF1 expression in muscle tissues.

Results: Anti-HSF1 was identified as a novel autoantibody by protein microarray and the seroreactivity was confirmed by immunoprecipitation, ELISA, immunoblot and dot blot assays. Anti-HSF1 autoantibodies were present in 64/581 (11.0%) IIM, 4/37 (10.8%) rheumatoid arthritis, 5/40 (12.5%) primary Sjögren's syndrome, 2/40 (5%) systemic lupus erythematosus, while largely negative in healthy controls. Anti-HSF1 autoantibodies were significantly associated with pruritus, hypergammaglobulinaemia, and elevated erythrocyte sedimentation rate in IIM patients. Anti-HSF1 autoantibodies were more prevalent in cancer-associated myositis (CAM) compared to non-CAM patients (17.2% vs. 7.5%, p=0.009), nevertheless were undetectable in cancer controls. Meanwhile, cross-sectional and longitudinal analyses revealed positive correlations between anti-HSF1 levels and disease activity in IIM patients without cancer. Additionally, increased expression of HSF1 was found in regenerating muscle cells of myositis muscle tissues.

Conclusions: These data reveal anti-HSF1 as a new autoantibody associated with CAM in IIM. The autoimmunity against HSF1 may be involved in the immunopathogenesis of myositis.
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December 2020

Exploring Road of Classification Criteria for Idiopathic Inflammatory Myopathy.

Chin Med J (Engl) 2018 Dec;131(23):2773-2775

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.

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http://dx.doi.org/10.4103/0366-6999.246082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278196PMC
December 2018

Survival rate, causes of death, and risk factors in systemic sclerosis: a large cohort study.

Clin Rheumatol 2018 Nov 18;37(11):3051-3056. Epub 2018 Sep 18.

Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), 11 Xizhimen South Street, Beijing, China.

To investigate the clinical pattern, survival rate, causes of death and risk factors in a large cohort of Chinese Han patients with systemic sclerosis (SSc). Inpatients treated from 2002 to 2014 were included in this study. Patients were classified into diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc-overlap syndrome groups. Data were analyzed using Chi-squared tests, Kaplan-Meier curves, log-rank tests, and Cox proportional hazards modeling. Among a total of 201 patients, dcSSc (50.2%) was the major subtype, followed by lcSSc (30.3%) and SSc-overlap (19.4%). Interstitial lung disease (ILD, 148/201, 74%) was the most frequent organ involvement. The overall survival rates were 98% and 95% at 5 and 10 years, respectively. The overall standard mortality ratio (SMR) was 2.22. The most common cause of death was ILD combined with infection (8/16, 50%), followed by kidney failure (2/16, 12.5%). On crude analysis, pulmonary hypertension, ILD, cardiac involvements, renal involvements, and digital ischemia were associated with poor prognosis. On multivariate analysis, pericardial effusion (p = 0.000) and digital ischemia (p = 0.016) were independent prognostic factors of death. The mortality rate of patients with SSc is mildly increased in comparison with the general population. ILD is the most common systemic involvement and the principal cause of death in SSc. Pericardial effusion and digital ischemia are independent factors associated with death.
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http://dx.doi.org/10.1007/s10067-018-4291-zDOI Listing
November 2018

Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies.

Int J Rheum Dis 2018 Aug;21(8):1619-1626

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China.

Objectives: Previous association studies have identified genetic variants in the human leukocyte antigen (HLA) complex as substantial risk factors for idiopathic inflammatory myopathies (IIMs). However, a great number of genes are located in the HLA region, and thus fine mapping is quite necessary.

Methods: Targeted capture sequencing were performed on the whole HLA region in 42 IIM patients and 24 healthy controls. A microarray analysis was applied to analyze gene expression profiles in additional 20 newly diagnosed IIM and five healthy controls.

Results: The HLA region was confirmed to be associated with IIMs in Chinese patients. By gene expression profiling and pathway analysis, several genes were identified as candidates for IIM risk factors, including HLA-A, HLA-B, HLA-DRB5, HLA-DRB1, HLA-DQA1, HLA-DQB1 and HLA-DQB2. Interestingly, p.Y107V of the HLA-DRB1 was predicted to be a potential causal non-synonymous variation for IIMs that may affect the antigen-binding groove of the HLA-II molecule.

Conclusions: Our data have revealed novel genetic variations in the HLA region of IIM patients and provide new insight into the pathogenesis and diagnosis of IIMs.
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http://dx.doi.org/10.1111/1756-185X.13350DOI Listing
August 2018

The prevalence and clinical significance of anti-PUF60 antibodies in patients with idiopathic inflammatory myopathy.

Clin Rheumatol 2018 Jun 15;37(6):1573-1580. Epub 2018 Mar 15.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, China.

Autoantibodies against poly-U-binding factor 60 kDa protein (PUF60) have been reported in Caucasian dermatomyositis (DM) patients. However, their clinical significance in idiopathic inflammatory myopathy (IIM) remains to be fully clarified. Our objective was to analyze the prevalence and clinical significance of anti-PUF60 antibodies in a large cohort of Chinese IIM patients. In our study, 388 IIM patients, 301 disease controls, and 167 healthy controls (HCs) were involved. An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum anti-PUF60 levels and was validated using immunoblotting methods. Unpaired Mann-Whitney U test and Spearman correlation analysis were used when appropriate. Anti-PUF60 antibodies were observed in IIM patients at a frequency of 10.6% (41/388). Subgrouping analysis revealed that the prevalence of anti-PUF60 antibodies was 10% in DM, 5.5% in polymyositis (PM), 10% in immune-mediated necrotizing myositis (IMNM), and 26.5% in myositis-overlap syndrome. Anti-PUF60 antibodies were also observed in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) patients at a positive rate of 17.3, 14.5, and 10.1% respectively. Intriguingly, anti-PUF60 antibodies were frequently observed in clinically amyopathic dermatomyositis (CADM) patients and DM patients without currently known myositis autoantibodies. Furthermore, DM patients with anti-PUF60 antibodies had higher prevalence of skin ulcerations. Moreover, longitudinal investigation in eight DM patients with anti-PUF60 antibodies revealed that the antibodies levels decreased with disease remission. Anti-PUF60 antibodies were nonspecific for myositis, since they could be detected in other rheumatic diseases. Further investigation of anti-PUF60 antibodies may reveal shared pathogenic pathways in systemic autoimmune disorders.
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http://dx.doi.org/10.1007/s10067-018-4031-4DOI Listing
June 2018

An efficacy analysis of whole-body magnetic resonance imaging in the diagnosis and follow-up of polymyositis and dermatomyositis.

PLoS One 2017 17;12(7):e0181069. Epub 2017 Jul 17.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objectives: To evaluate the value of whole-body magnetic resonance imaging (WBMRI) in diagnosing muscular and extra muscular lesions in patients with polymyositis (PM) and dermatomyositis (DM).

Methods: A retrospective analysis of WBMRI data from PM/DM patients who met the Bohan and Peter diagnostic criteria was performed. X2 test was used to compare the rate of positive diagnosis of newly diagnosed patients using WBMRI, serum creatine kinase test, and EMG. McNemar test was used to compare the performance of WBMRI and chest CT in detecting interstitial lung disease (ILD).

Results: The study included 129 patients (30 PM cases and 99 DM cases). Of them, 81.4% (105/129) showed a visible inflammatory muscular edema on their WBMRI; 29.5% (38/129) had varying degrees of fatty infiltration (9 cases with clear muscular atrophy). Of the 66 newly diagnosed patients, the positive rates of WBMRI, muscle biopsy, serum creatine kinase test and EMG were 86.4% (57/66), 92.4% (61/66), 71.2% (47/66) and 71.1% (32/45), respectively. There was no significant difference in the positive rates between WBMRI and muscle biopsy (X2 = 1.28, P = 0.258). The WBMRI had a higher positive rate than both serum creatine kinase test (X2 = 4.53, P = 0.033) and EMG (X2 = 3.92, P = 0.047). In addition to muscular changes, WBMRI also detected interstitial lung disease (ILD) in 38 cases (29.5%), osteonecrosis in 15 cases (11.6%), and neoplastic lesions (5 malignant; 7 benign) in 12 cases (9.3%). Of the 61 patients who underwent routine chest CT examinations, the WBMRI and CT revealed ILD in 29 cases and 35 cases respectively. There was no significant difference in the sensitivity between WBMRI and CT (p = 0.146).

Conclusions: WBMRI is a sensitive, non-invasive and efficient imaging method. It comprehensively displays the extent of muscular involvement in PM/DM patients, and it has the ability to diagnose other associated extra muscular diseases, such as ILD and systemic malignancy. WBMRI can also help screen steroid-induced osteonecrosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181069PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513424PMC
September 2017

A simple method for removing low-density granulocytes to purify T lymphocytes from peripheral blood mononuclear cells.

J Zhejiang Univ Sci B 2017 Jul;18(7):605-614

Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs.

Methods: The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions.

Results: Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs.

Conclusions: The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.
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http://dx.doi.org/10.1631/jzus.B1600064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498841PMC
July 2017

Value of whole-body magnetic resonance imaging for screening multifocal osteonecrosis in patients with polymyositis/dermatomyositis.

Br J Radiol 2017 May 29;90(1073):20160780. Epub 2017 Mar 29.

2 Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objective: To assess the value of coronal short-tau inversion recovery whole-body MRI (STIR-WBMRI) for screening osteonecrosis in patients with polymyositis (PM)/dermatomyositis (DM).

Methods: The imaging and medical records of 129 patients with PM/DM who met the Bohan and Peter diagnostic criteria were retrospectively analyzed. STIR-WBMRI was performed in all patients. 18 patients had follow-up STIR-WBMRI. 12 patients underwent regional knee and/or hip MRI while 25 patients underwent radiography of the lower extremities.

Results: STIR-WBMRI detected osteonecrosis in 15 (11.6%) patients. 38 joints were affected (mean, 2.5 per patient; range, 1-5 joints). Of the 38 joints affected by osteonecrosis, 33 had no clinical symptoms. Among the 12 patients who underwent regional MRI, STIR-WBMRI detected all 10 osteonecrotic sites seen on the regional MRI. The location, shape and size of the osteonecrotic lesions revealed on regional MRI were in accordance with those displayed on STIR-WBMRI. Of the 15 patients with osteonecrosis, 6 performed routine radiography of the affected joints and revealed no osteonecrotic lesions. Follow-up WBMRI detected new osteonecrosis in two patients whose first WBMRI revealed that there was no osteonecrosis in any skeleton.

Conclusion: In addition to displaying muscle inflammation, STIR-WBMRI can efficiently detect early multifocal osteonecrosis in the whole bodies of patients with PM/DM. Advances in knowledge: In patients with PM/DM, WBMRI which takes 12-15 min can display muscular involvement and detect early multisite osteonecrosis in the whole body at the same time. Osteonecrotic lesions revealed by WBMRI are in accordance with those displayed on regional WBMRI.
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http://dx.doi.org/10.1259/bjr.20160780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605105PMC
May 2017

The application of T2W SPIR-FLAIR in the diagnosis of hip synovitis in patients with spondyloarthritis.

Br J Radiol 2016 Dec 23;89(1068):20160566. Epub 2016 Sep 23.

4 Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objective: To investigate the feasibility and accuracy of T weighted spectral pre-saturation inversion recovery combined with fluid-attenuated inversion recovery (T2W SPIR-FLAIR) in the diagnosis of hip synovitis in patients with spondyloarthritis (SpA).

Methods: 10 volunteers underwent a T2W SPIR and 4 T2W SPIR-FLAIR sequence scans with different inversion times (TIs) to determine the optimum TI that could effectively suppress the intra-articular fluid signals. Hip MRI including T2W SPIR-FLAIR and enhanced T weighted (T1W) SPIR sequences was performed in 45 patients with SpA and totally 90 hips were evaluated. McNemar's test and Kappa test were used to compare the diagnostic results of synovitis between T2W SPIR-FLAIR and enhanced T1W SPIR.

Results: A TI of 2100 ms was selected as the optimum TI. 32 hips from 17 patients exhibited high signal intensity within the articular cavity on both T2W SPIR-FLAIR and enhanced T1W SPIR sequences, while only 3 hips showed high signals within the articular cavity on T2W SPIR-FLAIR. The remaining 55 hips did not show high signals within the articular cavity on both sequences. The T2W SPIR-FLAIR and enhanced T1W SPIR sequences had similar values in the diagnosis of hip synovitis (p = 0.25) and a high degree of diagnostic consistency (Kappa = 0.929).

Conclusion: T2W SPIR-FLAIR can effectively suppress the intra-articular fluid signals, while retaining the signals of thickened synovial membranes and can be used for the diagnosis of hip synovitis in patients with SpA. Advances in knowledge: The enhanced T1W SPIR is a classic sequence for synovitis diagnosis, but it requires the injection of contrast agents. The T2W SPIR-FLAIR and enhanced T1W SPIR sequences had similar values in the diagnosis of hip synovitis (p = 0.25) and a high degree of diagnostic consistency (Kappa = 0.929).
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http://dx.doi.org/10.1259/bjr.20160566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604922PMC
December 2016

Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis.

Sci Rep 2016 09 8;6:32818. Epub 2016 Sep 8.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.
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http://dx.doi.org/10.1038/srep32818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015085PMC
September 2016

Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study.

Clin Rheumatol 2016 Dec 23;35(12):2901-2908. Epub 2016 Aug 23.

Department of Rheumatology and Immunology, Beijing Hospital, Beijing, 100005, China.

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.
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http://dx.doi.org/10.1007/s10067-016-3383-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118386PMC
December 2016

A randomized, controlled trial of efficacy and safety of Anbainuo, a bio-similar etanercept, for moderate to severe rheumatoid arthritis inadequately responding to methotrexate.

Clin Rheumatol 2016 Sep 16;35(9):2175-83. Epub 2016 May 16.

Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200001, China.

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group-significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. -3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.
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http://dx.doi.org/10.1007/s10067-016-3302-1DOI Listing
September 2016

Primary Sjögren syndrome in Han Chinese: clinical and immunological characteristics of 483 patients.

Medicine (Baltimore) 2015 Apr;94(16):e667

From the Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing (YZ, YL, LW, XZ, Y-ZL, Y-YS, F-CZ); Department of Rheumatology and Immunology, Shanxi Medical University Second Hospital, Taiyuan (X-FL); Department of Rheumatology and Immunology, Beijing Hospital (C-BH); Department of Rheumatology and Immunology, China-Japan Friendship Hospital (G-CW); Department of Rheumatology and Immunology (X-WZ); Department of Rheumatology and Immunology, Peking University First Hospital, Beijing (ZZ); Department of Rheumatology and Immunology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou (XZ); Department of Rheumatology and Clinical Immunology, The First Hospital, China Medical University, Shenyang (W-GX); Department of Rheumatology and Clinical Immunology, SUN Yat-sen Memorial Hospital of SUN Yat-sen University, Guangzhou (LD); Department of Rheumatology and Immunology, The First Affiliated Hospital of Baotou Medical College, Baotou (Y-FW); Department of Immunology and Rheumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology,Wuhan (S-XH); Department of Rheumatology and Clinical Immunology, Affiliated Hospital of Inner Mongolia Medical College, Hohhot (H-BL); Department of Rheumatology and Clinical Immunology, General Hospital of Tianjin Medical University, Tianjin (LG); Department of Rheumatology and Immunology, The Affiliated Hospital of Medical College Qingdao University, Qingdao (BL); Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School (L-YS); Department of Rheumatology and Clinical Immunology, Jiangsu Provincial People's Hospital, Nanjing (M-JZ); Department of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (D-SD); Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China (S-HZ).

The epidemiological characteristics of Sjögren syndrome (SS) are significantly varied in different countries. We conducted the present study to survey the epidemiological characteristics of primary SS in China. We recruited 483 primary SS patients from 16 Chinese medical centers nationwide from January 2009 to November 2011 and assessed salivary and lacrimal gland dysfunction, organ involvement, and autoimmunity in these patients. The cohort included 456 women and 27 men (ratio, 17:1; mean age at onset, 42 ± 11 years; median age at diagnosis, 49 years; range, 41-56 years). Male patients showed a lower frequency of xerophthalmia (37.0% vs 60.7%) and a higher frequency of arthritis (40.7% vs 16.4%). Young-onset patients showed a higher frequency of low C3 levels (57.7% vs 36.3%) and pancytopenia (22.2% vs 8.8%). Patients with systemic involvement had a higher frequency of immunoglobulin A (IgA) (39.4% vs 22.5%) and immunoglobulin M (IgM) (12.4% vs 37.9%). Patients with pulmonary involvement had a higher parotid enlargement (21.4% vs 10.2%), purpura (12.1% vs 5.7%) and higher anti-La/SS-B (61.7% vs 41.8%), immunoglobulin G (IgG) (80.7% vs 64.6%) and IgA (48.9% vs 30.6%) levels. Patients with anti-Ro/SSA antibodies had more frequent exocrine gland symptoms and some extraglandular symptoms and immunological alterations. Compared with previous studies performed in other countries, SS patients in China showed particular clinical manifestation, systemic involvement, and immunological alterations.
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http://dx.doi.org/10.1097/MD.0000000000000667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602699PMC
April 2015

Elevated Serum Levels of Soluble CD163 in Polymyositis and Dermatomyositis: Associated with Macrophage Infiltration in Muscle Tissue.

J Rheumatol 2015 Jun 15;42(6):979-87. Epub 2015 Apr 15.

From the Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.Q.L. Peng, MS; Y.L. Zhang, MD; X.M. Shu, MD; H.B. Yang, MS; L. Zhang, MD; F. Chen, MD; X. Lu, MD; G.C. Wang, MD, Department of Rheumatology, China-Japan Friendship Hospital.

Objective: To investigate serum levels of soluble CD163 (sCD163) in patients with polymyositis (PM) and dermatomyositis (DM), and to correlate these to clinical manifestations and laboratory data.

Methods: Serum levels of sCD163 were detected in 24 patients with PM, 84 patients with DM, and 46 healthy controls by using the ELISA method. Immunohistochemistry staining of macrophage infiltration in muscle tissue using anti-CD163 monoclonal antibody was conducted on muscle biopsy specimens from 13 patients with PM and 17 with DM.

Results: Serum levels of sCD163 were significantly increased in patients compared with healthy controls (p < 0.001). Patients with interstitial lung disease (ILD) had statistically higher sCD163 levels than patients without ILD (p < 0.001). High serum sCD163 levels were associated with increased incidence of antinuclear antibody (p < 0.05), higher serum levels of immunoglobulin G (p < 0.01) and immunoglobulin A (p < 0.05), and increased erythrocyte sedimentation rates (p < 0.01). Serum sCD163 levels were inversely correlated with CD3+ T cell counts in peripheral blood of patients (r = -0.306, p < 0.01). Cross-sectional assessment and longitudinal study revealed a significant correlation between serum sCD163 levels and disease activity. Patients with high serum sCD163 levels showed a higher incidence of CD163+ macrophage infiltration in muscle tissue than patients with normal sCD163 levels (chi-square value = 10.804, p < 0.01).

Conclusion: Serum levels of sCD163 were significantly elevated and correlated with disease severity in patients with PM/DM, suggesting serum sCD163 as a promising biomarker in the disease evaluation of PM/DM. Our finding of elevated serum sCD163 levels associated with muscle macrophage infiltration highlights the role activated macrophage plays in the pathogenesis of PM/DM.
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http://dx.doi.org/10.3899/jrheum.141307DOI Listing
June 2015

Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

Clin Rheumatol 2015 Feb 22;34(2):221-30. Epub 2014 Nov 22.

Department of Rheumatology and Immunology, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China.

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.
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http://dx.doi.org/10.1007/s10067-014-2828-3DOI Listing
February 2015

Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial.

Clin Rheumatol 2016 Jan 14;35(1):165-73. Epub 2014 Jun 14.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China.

This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.
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http://dx.doi.org/10.1007/s10067-014-2701-4DOI Listing
January 2016

B-cell activating factor as a serological biomarker for polymyositis and dermatomyositis.

Biomark Med 2014 ;8(3):395-403

Department of Rheumatology, China-Japan Friendship Hospital, Ying Hua East Road, Chao Yang District, Beijing 100029, China.

Aim: To investigate serum levels of B-cell activating factor (BAFF) in the patients with polymyositis (PM) and dermatomyositis (DM), and to systematically examine the association between serum BAFF levels and disease activity in PM/DM patients.

Patients & Methods: A cross-sectional analysis included 92 PM/DM patients and 25 healthy control subjects. A longitudinal study followed 24 patients. Serum BAFF concentrations were detected by the ELISA method.

Results: Serum BAFF levels in PM/DM patients were significantly higher than those in healthy controls. A cross-sectional assessment revealed a modest correlation between serum BAFF levels and global disease activity and a mild correlation between serum BAFF levels and muscle disease activity. The longitudinal study showed that serum BAFF levels modestly correlated with global disease activity and muscle disease activity.

Conclusion: Resulting data showed high serum BAFF levels in PM/DM patients and suggested BAFF as a serological biomarker for PM/DM disease activity.
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http://dx.doi.org/10.2217/bmm.13.124DOI Listing
November 2014

Expression of tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 in patients with polymyositis and dermatomyositis.

Arthritis Res Ther 2014 Jan 27;16(1):R26. Epub 2014 Jan 27.

Introduction: The aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations.

Methods: Serum levels of TWEAK were detected in 98 PM/DM patients and 37 healthy controls by using the ELISA method. Total RNA isolated from fresh-frozen muscle tissue samples of 36 PM/DM patients and 10 healthy controls were used for analyzing the mRNA levels of TWEAK and Fn14 by quantitative reverse transcription polymerase chain reaction (RT-PCR). Immunofluorescence staining of TWEAK and Fn14 was conducted on muscle biopsy specimens from 23 PM/DM patients and seven healthy controls.

Results: Serum levels of TWEAK were significantly decreased in the PM/DM patients compared to those in the healthy controls (P < 0.001), and serum TWEAK levels negatively correlated with serum CD163 levels in PM/DM patients (r = -0.49, P < 0.001). The expression of Fn14 mRNA was significantly increased in the muscle tissue of PM/DM patients than in the muscle tissue of healthy controls (P < 0.01), whereas the expression of TWEAK mRNA in PM/DM patients was not statistically different from that of the healthy controls (P > 0.05). Fn14 mRNA levels in muscle tissue positively correlated with muscle disease activity (r = 0.512, P < 0.01). Patients with oropharyngeal dysphagia had significantly higher Fn14 mRNA levels than patients without oropharyngeal dysphagia (P < 0.05). The results of immunofluorescence staining showed that 19 out of 23 PM/DM patients were TWEAK-positive, and 20 out of 23 PM/DM patients were Fn14-positive. No detectable expressions of TWEAK or Fn14 were observed in the healthy controls.

Conclusions: TWEAK-Fn14 axis may be involved in the pathogenesis of PM/DM. Further understanding of TWEAK-Fn14 function in PM/DM may help to define therapeutic targets for PM/DM.
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http://dx.doi.org/10.1186/ar4454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978894PMC
January 2014

National survey of knowledge, attitude and practice of fibromyalgia among rheumatologists in China.

Int J Rheum Dis 2013 Jun 4;16(3):258-63. Epub 2013 Apr 4.

Department of Rheumatologyand Immunology, People's Hospital, Peking University, Beijing, China.

Aim: 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.

Method: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1111/1756-185X.12055DOI Listing
June 2013

Left ventricular diastolic dysfunction -- early cardiac impairment in patients with polymyositis/dermatomyositis: a tissue Doppler imaging study.

J Rheumatol 2013 Sep 1;40(9):1572-7. Epub 2013 Aug 1.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objective: To investigate early cardiac involvement in patients with polymyositis/dermatomyositis (PM/DM), and to evaluate the risk factors for early cardiac impairment.

Methods: The study population included 46 patients with PM/DM who did not have overt cardiovascular manifestations and 21 age- and sex-matched healthy controls. Traditional echocardiography and tissue Doppler imaging (TDI) were used to evaluate cardiac function in both groups. Clinical characteristics were recorded. Multivariate logistics regression analysis was applied to investigate risk factors for early cardiac impairment in patients with PM/DM.

Results: No significant difference was found between patients and controls by traditional echocardiography. However, compared to controls, PM/DM patients had a significantly lower ratio of early diastolic mitral annulus velocity to late diastolic mitral annulus velocity (Em/Am; 1.23 ± 0.52, 1.79 ± 0.37, respectively; t = -4.485, p < 0.001) and a higher ratio of peak early diastolic transmitral flow velocity to Em (E/Em; 8.26 ± 2.57, 6.76 ± 1.17; t = 3.287, p < 0.05) as found by TDI measurements. There was no significant difference between the TDI variables of patients with PM and DM. The multivariate regression analysis showed that female sex (OR 11.044, 95% CI 1.066-114.357, p = 0.044), late onset (OR 1.157, 95% CI 1.047-1.278, p = 0.004), and duration of disease (OR 1.060, 95% CI 1.008-1.115, p = 0.023) were risk factors for abnormal left ventricular filling pressures.

Conclusion: TDI is useful for detecting early cardiac impairment in patients with PM/DM. Left ventricular diastolic dysfunction is an early feature of cardiac involvement. Female sex, late onset, and long course of disease are 3 independent risk factors for predicting left ventricular diastolic dysfunction in patients with PM/DM.
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http://dx.doi.org/10.3899/jrheum.130044DOI Listing
September 2013

The application of MR imaging in the detection of hip involvement in patients with ankylosing spondylitis.

Eur J Radiol 2013 Sep 13;82(9):1487-93. Epub 2013 May 13.

Department of Radiology and Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: To investigate the changes in hip MR imaging, evaluate the frequency of hip involvement and compare the value of clinical symptoms, radiographs, and MR imaging in the detection of hip involvement in patients with ankylosing spondylitis (AS).

Methods: Anteroposterior radiographs of the pelvis, MR imaging of the hip and clinical evaluation were undertaken in 58 patients with definite AS. All patients were followed up 3 years. Annual radiographs and clinical evaluation were carried out. The imaging data were independently assessed by two experienced radiologists who were blinded to patient identity and clinical characteristics. Based on the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-hip) scoring system, BASRI-hip scores ≥ 2 were defined as radiological hip involvement. On MR imaging, both acute and chronic inflammatory changes were considered positive signs for hip involvement. Symptomatic hip involvement was defined as current or past pain or limitation of the hip movement. The statistical analysis was performed using the χ(2) test for comparison of sensitivity among clinical symptoms, radiographs, and MR imaging in the detection of hip involvement and the Student's t-test for comparison of disease duration between with and without hip involvement. A P value <0.05 was considered to be statistically significant. For interpreting MRI and radiographs, the percentage of agreement between the two assessors and the kappa coefficients were calculated.

Results: On MR imaging, positive changes were detected in 86 (74.1%) hips among 116 hips in all 58 patients. Joint effusion was observed in 73 (62.9%) hips; 23 out of 27 patients who underwent fat-saturated contrast-enhanced T1-weighted sequences had abnormal synovial enhancement in bilateral hips. The other abnormal MR findings included subchondral bone marrow edema in 35 (30.2%) hips, enthesitis in 22 (19.0%) hips, fatty accumulation of the bone marrow in 28 (24.1%) hips, bone erosive destruction in 32 (27.6%) hips, and joint-space narrowing in 4 (3.4%) hips. Based on the BASRI-hip scoring system, 68, 24, 18, 6 and 0 hips had no, suspicious, mild, moderate or severe damage on conventional radiographs of the pelvis, respectively. Thirty-five hips in 20 patients had current or past pain or limitation. The proportion of hip involvement according to MR imaging, radiographs, and clinical symptoms was 74.1% (86/116), 20.7% (24/116), and 30.2% (35/116), respectively. MR imaging yielded higher values than radiographs and clinical symptoms in the detection of hip involvement in patients with AS (χ(2)=66.45 and 44.93, P <0.05). Interreader reliability for interpretation of findings was acceptable for both MRI and radiographs. During follow-up, radiological hip involvement were found in 10 hips with BASRI-hip scores ≤ 1 at baseline and clinical symptoms appeared in 15 sides of the original asymptomatic hip. On baseline MR imaging, inflammatory changes were seen in all hips which appeared symptoms and/or radiological involvement both at baseline and during follow-up.

Conclusion: The proportion of hip involvement is much higher than that suggested by radiographic changes and clinical symptoms. MR imaging is superior to conventional radiographs and clinical symptoms in the detection of hip involvement. Joint effusion and synovial enhancement caused by synovitis are the commonest hip findings on MR imaging in patients with AS.
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http://dx.doi.org/10.1016/j.ejrad.2013.03.020DOI Listing
September 2013

[Surfactant proteins-A and D as important serum markers for interstitial lung disease in patients with polymyositis or dermatomyositis].

Zhonghua Yi Xue Za Zhi 2012 Aug;92(31):2182-5

Graduate School, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Objective: To explore the possible diagnostic values of serum surfactant protein-A (SP-A) and surfactant protein-D (SP-D) for interstitial lung diseases (ILD) in patients with polymyositis or dermatomyositis (PM/DM).

Methods: Serum MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 100 adult PM/DM patients, 20 patients with pulmonary infection and 42 healthy controls. And the association with their clinical features and serum levels of SP-A and SP-D was analyzed.

Results: The serum levels of SP-A and SP-D in the PM/DM patients with ILD were both significantly higher than those without ILD and healthy controls (all P < 0.01) while there were no significance differences with those with infectious lung diseases (P > 0.05). The sensitivity of serum abnormal levels of SP-A, SP-D and combination of SP-A and SP-D for ILD in PM/DM patients were 66.1%, 64.3% and 80.0% and the specificity 72.7%, 72.7% and 70.2% respectively. The serum levels of SP-A were positively correlated with serum ferritin and C-reactive protein (CRP) and negatively with percent carbon monoxide diffusing capacity (DLCO%) (r = -0.474, P < 0.05), VC% (r = -0.404, P < 0.05) while the serum levels of SP-D were negatively correlated with circulating CD3+T cells (r = -0.244, P < 0.05) and CD4+T cells (r = -0.277, P < 0.05) in PM/DM patients. Furthermore, SP-A was an independent risk factor for death of ILD in PM/DM (OR 1.032, 95%CI 1.006 - 1.059, P < 0.05).

Conclusion: SP-A and SP-D may be potential useful serum markers for the diagnosis of ILD in PM/DM patients. And the combined detection of SP-A and SP-D offers a higher sensitivity than either marker alone. As a risk factor, serum SP-A can predict the prognosis of PM/DM patients with ILD.
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August 2012

Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis.

Clin Rheumatol 2012 Dec 30;31(12):1691-7. Epub 2012 Aug 30.

Department of rheumatology, China-Japan Friendship hospital, Yinghua East road, Chaoyang district, Beijing, China.

Peripheral blood lymphocyte subsets were determined by flow cytometry in 89 Chinese patients with polymyositis (PM) and dermatomyositis (DM). We aimed to investigate the clinical significance of peripheral blood lymphocyte subsets in PM/DM. Patients with active DM showed significant decreases in numbers of CD3(+) cells, CD3(+)CD4(+) cells, and CD3(+)CD8(+) cells, as compared to patients with inactive DM and healthy controls (P < 0.05). CD3(+) and CD3(+)CD4(+) cell counts were significantly lower in DM before treatment, compared with after treatment (t = -5.714 and -3.665, P < 0.05). Counts of CD3(+) cells, CD3(+)CD4(+) cells, CD3(+)CD8(+) cells, and CD19(+)CD5(-) cells were all correlated with the total disease activity score as determined by the Myositis Disease Activity Assessment Visual Analogue Scale (P < 0.05). The decreased number of CD3(+) cells and the decreased percentage of CD3(+)CD4(+) cells were additionally correlated with the presence of interstitial lung disease in PM/DM (P < 0.05). The presence of levels of CD3(+)CD8(+) cells was risk factor for death (b = -0.011, OR = 0.989, P < 0.05). The identification of peripheral blood T lymphocyte subsets in PM/DM appears to be useful as a reference marker in the evaluation of clinical disease activity, and be useful in the comprehensive assessment of clinical lung involvement. A decrease in CD8(+) T cells may predict a poor outcome in patients with PM/DM.
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http://dx.doi.org/10.1007/s10067-012-2075-4DOI Listing
December 2012
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