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Deng C.,Peking Union Medical College | Deng C.,Key Laboratory of Rheumatology and Clinical Immunology | Zhang S.,Peking Union Medical College | Zhang S.,Key Laboratory of Rheumatology and Clinical Immunology | And 16 more authors.
PLoS ONE | Year: 2017

Background A reference interval (RI) for the circulating concentration of anti-dsDNA antibody is essential for clinicians to interpret laboratory results and make clinical decisions. Therefore, we aimed to establish the RI for anti-dsDNA antibody in the Chinese Han population. Methods This study was designed and carried out in accordance with guideline C28-A3, which is proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. A total of 2,880 apparently healthy individuals were enrolled using a posteriori sampling. These individuals were recruited from four hospitals, representing the Han populations of north, south, east, and west China. Serum anti-dsDNA antibody levels were measured using the three analytical systems AESKU, EUROIMMUNE, and INOVA, which are the most commonly used systems in China. Individuals were stratified by gender, age, and region, and the RIs were obtained by nonparametric methods. Results Gender-specific RIs for serum anti-dsDNA antibody in the Chinese Han population were established. Conclusion This is the first exploration of the RI for anti-dsDNA antibody in the Chinese Han population. We have established gender-specific RIs for each assay method commonly used in China. © 2017 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Peng L.,Peking Union Medical College | Peng L.,Key Laboratory of Rheumatology and Clinical Immunology | Ma W.,Peking University | Yi F.,Peking University | And 13 more authors.
Journal of Rheumatology | Year: 2014

Objective. Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS. Methods. Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals. Compared to the healthy participants, 202 miRNA were upregulated and 180 were downregulated in the patients with pSS. To confirm this finding, a set of regulated miRNA was further examined in a large patient group, using quantitative reverse transcriptase-PCR assays. Results. MiR-181a was the miRNA that most profoundly differed between patients with pSS and healthy individuals; however, similar miRNA-181a expression profiles were found in groups with different disease phenotypes. Together, these observations suggested that an elevated miRNA-181a level is a general phenomenon in Chinese patients with pSS. Conclusion. In addition to the elevated miR-181a levels, our study led to the speculation that elevated miR-181a levels in the PBMC of these patients compromise the maturation of B cells, enabling them to recognize and attack autoantigens and resulting in disease phenotypes. In addition to the regulation of human miRNA, many virus-derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting that viral infection of PBMC plays a role in this disease. Copyright © 2014. All rights reserved.


Chen Z.,Peking Union Medical College | Chen Z.,Key Laboratory of Rheumatology and Clinical Immunology | Li M.-T.,Peking Union Medical College | Li M.-T.,Key Laboratory of Rheumatology and Clinical Immunology | And 11 more authors.
PLoS ONE | Year: 2014

Objective: Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. Methods: A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 20002January 2012. Risk factors for SLErelated PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. Results: The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (<22 g/ l) and 24-hour urine protein (<0.8 g/24 h) had high specificity, positive predictive value, negative predictive value, and positive likelihood ratio, a low negative likelihood ratio and no significant reduction in sensitivity. High dosage of glucocorticosteroid combined with cyclophosphomide were mostly prescribed for SLE-related PLE. Conclusion: SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis. © 2014 Chen et al.


Xu L.,Tsinghua University | Xu L.,Collaborative Innovation Center for Infectious Diseases | Xu L.,Peking Union Medical College | Xu L.,Key Laboratory of Rheumatology and Clinical Immunology | And 12 more authors.
Journal of Leukocyte Biology | Year: 2015

Sphingolipid- and cholesterol-rich lipid raft microdomains are important in the initiation of BCR signaling. Although it is known that lipid rafts promote the coclustering of BCR and Lyn kinase microclusters within the B cell IS, the molecular mechanism of the recruitment of lipid rafts into the B cell IS is not understood completely. Here, we report that the synaptic recruitment of lipid rafts is dependent on the cytoskeleton-remodeling proteins, RhoA and Vav. Such an event is also efficiently regulated by motor proteins, myosin IIA and dynein. Further evidence suggests the synaptic recruitment of lipid rafts is, by principle, an event triggered by BCR signaling molecules and second messenger molecules. BCR-activating coreceptor CD19 potently enhances such an event depending on its cytoplasmic Tyr421 and Tyr482 residues. The enhancing function of the CD19-PI3K module in synaptic recruitment of lipid rafts is also confirmed in human peripheral blood B cells. Thus, these results improve our understanding of the molecular mechanism of the recruitment of lipid raft microdomains in B cell IS. © Society for Leukocyte Biology.


Chen Z.,Peking Union Medical College | Chen Z.,Key Laboratory of Rheumatology and Clinical Immunology | Chen Z.,Fujian Medical University | Li M.-T.,Peking Union Medical College | And 15 more authors.
Clinical Rheumatology | Year: 2015

With this study, we provide insight into the clinical characteristics, laboratory characteristics, and organ damage associated with incomplete lupus syndromes (ILE) and search for predictors of organ damage in ILE. A retrospective chart review was performed on 77 hospitalized patients with ILE. The control patient group comprised 2104 systemic lupus erythematosus (SLE) patients who were entered into the Chinese SLE Treatment and Research group (CSTAR). The Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI) was used to classify damage features. Based on their SDI score, ILE patients were divided into SDI > 0 and SDI = 0 groups. The percentages of anti-SSA-seropositive (54.5 %) and anti-RNP-seropositive (24.7 %) patients with ILE were higher than those found among the SLE patients from CSTAR (p < 0.001). The mean SDI score was 0.66 (range 0–2), and a damage score greater than 0 was present in 41 (53.3 %) patients. The most prevalent damage category was pulmonary damage, present in 17 (22.1 %) patients. Peripheral vascular damage occurred in individuals who were significantly older than those who had musculoskeletal damage (p = 0.031). The subgroup with SDI > 0 had a higher mean age (36.8 ± 2.04 years) than those with SDI = 0 (30.8 ± 2.08 years; p = 0.044). The mean SLEDAI score in the SDI > 0 patient group (8.2 ± 0.74) was higher than that of the SDI = 0 group (4.8 ± 0.54; p = 0.001). ILE patients may include a subset that is likely to experience progressive organ damage. Organ damage was more common in patients of older age and with high SLEDAI scores. © 2015, International League of Associations for Rheumatology (ILAR).


Xianbin W.,Peking Union Medical College | Xianbin W.,Key Laboratory of Rheumatology and Clinical Immunology | Xianbin W.,Yantai Yuhuangding Hospital | Mingyu W.,Peking Union Medical College | And 10 more authors.
Medicine (United States) | Year: 2015

This article aims to analyze the frequency and clinical characteristics of peripheral neuropathy (PN) in patients with systemic lupus erythematosus (SLE). A total of 4924 SLE patients admitted to the Peking Union Medical College Hospital, Beijing, China, from January 1995 to September 2013 were included in this retrospective analysis. The individuals designated as control patients were selected from the pool of SLE patients without PN using the systematic sampling method of 1:2 during the same time. The prevalence of SLE-associated PN (SLE-PN) in SLE patients was 1.5% (73/4924). Seventy-nine cases of PN affected 73 patients and 6 of these patients (8.2%) presented with 2 types of PN. Among the 7 types of PN, polyneuropathy was the most frequent and was diagnosed in 47 cases (59.5%); the remaining patients suffered from mononeuropathy (13.9%), cranial neuropathy (12.7%), myasthenia gravis (10.1%), autonomic neuropathy (2.5%), or acute inflammatory demyelinating polyradiculoneuropathy (1.3%). Five patients developed PN before the onset of SLE (3 out of 5 patients had myasthenia gravis). The most common PN-related symptoms were myasthenia and numbness (50.6%), followed by pain in affected regions (35.9%). PN symptoms were relieved in a majority of the patients (76.7%) after treatment. Compared with non-SLE-PN patients, patients with SLE-PN had a higher frequency of fever (65.8% vs 45.9%, P<0.01), mucocutaneous involvement (73.9% vs 36.3%, P<0.01), arthritis (42.5% vs 28.1%, P<0.05), myositis (17.8% vs 5.5%, P<0.01), and central nervous system involvement (38.4% vs 21.9%, P<0.05) as well as being positive for the anti-Sm antibody (31.4% vs 18.8%), immunoglobulin G (IgG) elevation (53.6% vs 37.1%, P<0.01), and reduction in complement 3 (54.8% vs 36.9%, P<0.05). A statistically significant difference was found between the Systemic Lupus Erythematosus Disease Activity Index scores in SLE-PN patients compared with the non-SLE-PN patients (P<0.05). Multivariate logistic regression showed that the only risk factor for PN was IgG elevation (odds ratio=2.553, 1.224-5.327, P=0.012). The prevalence of PN in SLE occurs more frequently in patients with an active form of the disease. IgG elevation is a risk factor for SLE-PN and should be assessed in these patients. Young female patients with myasthenia gravis should be closely monitored for the development of SLE. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Zhang L.-N.,Peking Union Medical College | Zhang L.-N.,Key Laboratory of Rheumatology and Clinical Immunology | Shi T.-Y.,Peking Union Medical College | Shi T.-Y.,Key Laboratory of Rheumatology and Clinical Immunology | And 37 more authors.
Hepatology | Year: 2013

The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long-term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver-related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow-up of 5.8 years (range, 1.3-14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long-term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. © 2013 American Association for the Study of Liver Diseases.


Zhang L.,Peking Union Medical College | Shen M.,Key Laboratory of Rheumatology and Clinical Immunology | Zhang F.,Key Laboratory of Rheumatology and Clinical Immunology | Tang F.,Key Laboratory of Rheumatology and Clinical Immunology
Rheumatology International | Year: 2014

The aim of this study was to analyze the characteristics of patients with diffuse connective tissue diseases (CTDs) complicated by pneumomediastinum and identify the risk factors associated with increased mortality in these patients. Twenty-eight patients with CTD-associated pneumomediastinum, who were admitted to our hospital from January 1997 to June 2012, were prospectively studied. Their demographic characteristics, time to death, and potential risk factors were assessed. Survival curves were depicted by the Kaplan–Meier method. Univariate and multivariate survival analyses were performed by Cox regression. Of the 28 patients, 21 had dermatomyositis; two, polymyositis; three, systemic lupus erythematosus; one, polyarteritis nodosa; and one, undifferentiated CTD. The mean follow-up period was 1,461 days (54–5,264). The cumulative estimated Kaplan–Meier survival rate was 68 % at 1 week, 50 % at 1 month, and 43 % at 1 year. According to univariate analysis, higher serum albumin level (HR 0.87, 95 % CI 0.78–0.98), “slow air leak” (defined as time to progression of dyspnea [newly acquired respiratory failure, mechanical ventilation required, or decrease in PaO2 >30 mmHg after pneumomediastinum]) >3 days (HR 0.07, 95 % CI 0.02–0.34), and early initiation of immunosuppressive agents (within 1 month of steroid therapy; HR 0.27, 95 % CI 0.09–0.81) were associated with better prognosis. Final regression analysis revealed that slow air leak was associated with a lower mortality risk. We found that slow air leak was independently associated with better prognosis. Furthermore, most patients (86 %) who survived for at least 1 month following the pneumomediastinum event subsequently survived beyond 1 year. © 2014, Springer-Verlag Berlin Heidelberg.


Zhang L.,Peking Union Medical College | Zhang L.,Key Laboratory of Rheumatology and Clinical Immunology | Zhu Y.-L.,Peking Union Medical College | Li M.-T.,Peking Union Medical College | And 21 more authors.
Chinese Medical Journal | Year: 2015

Background: Myocarditis is an uncommon but serious manifestation of systemic lupus erythematosus (SLE). This study aimed to investigate clinical characteristics and outcomes of lupus myocarditis (LM) and to determine risk factors of LM in hospitalized Chinese patients with SLE. Methods: We conducted a retrospective case–control study. A total of 25 patients with LM from 2001 to 2012 were enrolled as the study group, and 100 patients with SLE but without LM were randomly pooled as the control group. Univariable analysis was performed using Chi-square tests for categorical variables, and the Student’s t-test or Mann–Whitney U-test was performed for continuous variables according to the normality. Results: LM presented as the initial manifestation of SLE in 7 patients (28%) and occurred mostly at earlier stages compared to the controls (20.88 ± 35.73 vs. 44.08 ± 61.56 months, P = 0.008). Twenty-one patients (84%) experienced episodes of symptomatic heart failure. Echocardiography showed that 23 patients (92%) had decreased left ventricular ejection fraction (<50%) and all patients had wall motion abnormalities. A high SLE Disease Activity Index was the independent risk factor in the development of LM (odds ratio = 1.322, P < 0.001). With aggressive immunosuppressive therapies, most patients achieved satisfactory outcome. The in-hospital mortality was not significantly higher in the LM group than in the controls (4% vs. 2%, P = 0.491). Conclusions: LM could result in cardiac dysfunction and even sudden death. High SLE disease activity might potentially predict the occurrence of LM at the early stage of SLE. Characteristic echocardiographic findings could confirm the diagnosis of LM. Early aggressive immunosuppressive therapy could improve the cardiac outcome of LM. © 2015 Chinese Medical Journal.

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