Publications by authors named "Jiuliang Zhao"

87 Publications

The LPS induced pyroptosis exacerbates BMPR2 signaling deficiency to potentiate SLE-PAH.

FASEB J 2021 Dec;35(12):e22044

Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Pulmonary arterial hypertension (PAH) is a common and fatal complication of systemic lupus erythematosus (SLE). Whether the BMP receptor deficiency found in the genetic form of PAH is also involved in SLE-PAH patients remains to be identified. In this study, we employed patient-derived samples from SLE-associated PAH (SLE-PAH) and established comparable mouse models to clarify the role of BMP signaling in the pathobiology of SLE-PAH. Firstly, serum levels of LPS and autoantibodies (auto-Abs) directed at BMP receptors were significantly increased in patients with SLE-PAH compared with control subjects, measured by ELISA. Mass cytometry was applied to compare peripheral blood leukocyte phenotype in patients prior to and after treatment with steroids, which demonstrated inflammatory cells alteration in SLE-PAH. Furthermore, BMPR2 signaling and pyroptotic factors were examined in human pulmonary arterial endothelial cells (PAECs) in response to LPS stimulation. Interleukin-8 (IL-8) and E-selectin (SELE) expressions were up-regulated in autologous BMPR2 endothelial cells and siBMPR2-interfered PAECs. A SLE-PH model was established in mice induced with pristane and hypoxia. Moreover, the combination of endothelial specific BMPR2 knockout in SLE mice exacerbated pulmonary hypertension. Pyroptotic factors including gasdermin D (GSDMD) were elevated in the lungs of SLE-PH mice, and the pyroptotic effects of serum samples isolated from SLE-PAH patients on PAECs were analyzed. BMPR2 signaling upregulator (BUR1) showed anti-pyroptotic effects in SLE-PH mice and PAECs. Our results implied that deficiencies of BMPR2 signaling and proinflammatory factors together contribute to the development of PAH in SLE.
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http://dx.doi.org/10.1096/fj.202100851RRDOI Listing
December 2021

Relapse rates and risk factors for unfavorable neurological prognosis of transverse myelitis in systemic lupus erythematosus: A systematic review and meta-analysis.

Autoimmun Rev 2021 Nov 16:102996. Epub 2021 Nov 16.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Beijing 100730, China; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China.

Background: Transverse myelitis (TM) is a rare but severe systemic lupus erythematosus (SLE) phenotype. To date, the prognostic factors of SLE-associated TM are far less well-studied. There is also controversial data on the association of antiphospholipid antibodies (aPLs), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, longitudinal extensive transverse myelitis (LETM), and lower complement levels with the outcome of TM. We aim to review the potential prognostic factors and integrate the relapse rates of observational studies for SLE-associated TM.

Method: To review the prognosis for SLE-associated TM, relevant articles published up to July 30, 2021, were comprehensively and systematically identified from PubMed, EMBASE, and Web of Science databases. Five studies encompassing 280 patients with SLE-related TM were included in the meta-analysis. Raw data were obtained from three studies.

Results: The risk factors for unfavorable neurological outcomes (including demographic features, clinical characteristics, laboratory data, and comorbidity), A grade of A, B, or C on the American Spinal Injury Association Impairment Scale (AIS) at the onset of TM is associated with poor prognosis (OR: 56.05, 95% CI: 6.29-499.25, P < 0.001). A high rate of hypoglycorrhachia was also correlated with a worse prognosis (OR: 10.78, 95% CI: 3.74-31.07, P < 0.001). No noticeable relationships were revealed between a poor outcome and levels of antiphospholipid antibodies (aPLs) and their subtypes (anticardiolipin antibody [aCL], anti-β2-glycoprotein I (anti-β2GPI], lupus anticoagulant [LA]). The pooled 1-, 3- and 5-year relapse rates were 22% (95% CI: 0.13-0.31), 34% (95% CI: 0.22-0.47) and 36% (95% CI: 0.14-0.58), respectively. No significant publication bias was found.

Conclusion: A grade of A, B, or C on the AIS at initial TM and hypoglycorrhachia were found to be related to worse prognosis in patients with SLE-associated TM. Notably, aPLs and their subtypes may not suggest poor neurological outcomes. The long-term relapse rate of patients with SLE-associated TM was relatively high. We strongly recommend that treatment be stratified based on the initial severity of myelitis. For patients with severe myelitis, early intensive therapy (rituximab (RTX), plasma exchange (PLEX), or anti-IL-6 agents) should be initiated as soon as possible, in addition to steroid pulse therapy.
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http://dx.doi.org/10.1016/j.autrev.2021.102996DOI Listing
November 2021

Clinical Characteristics and Prognoses of Patients With Systemic Lupus Erythematosus Hospitalized for Pulmonary Infections.

Front Med (Lausanne) 2021 29;8:732681. Epub 2021 Sep 29.

Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

To identify factors associated with mortality in SLE patients who were hospitalized for pulmonary infections (PIs). This single-center retrospective study analyzed the characteristics and risk factors for mortality in 95 SLE patients hospitalized for PIs. Ninety-five SLE patients had 97 episodes of hospitalization for PIs, and 33 of these episodes (34.02%) led to death. Death from PI was associated with a higher neutrophil count (6.30 vs. 4.201 × 10/L, < 0.01), immunoglobulin G (6.20 vs. 9.82 g/L, = 0.01), serum creatinine (126.00 vs. 73.00 μmol/L, = 0.01), proteinuria (2.99 vs. 0.54 g/day, < 0.01), cardiopulmonary involvement (57.58 vs. 34.38%, < 0.05), SLE disease activity index (SLEDAI; 11.00 vs. 6.00, < 0.05), and opportunistic infections (78.79 vs. 45.31%, < 0.05). Demographic characteristics, antibody/complements, bacterial infection, and primary treatment before infection (including corticosteroid and immunosuppressants) had no effect. Multivariate analysis indicated cardiopulmonary involvement (HR: 2.077; 95%CI: 1.022-4.220; = 0.043) and opportunistic infection (HR: 2.572; 95%CI: 1.104-5.993; = 0.029) were independent risk factors for mortality. High-dose steroid pulse therapy (HR: 0.982; 95%CI: 0.410-2.350; = 0.982) and first-line immunosuppressant therapy (HR: 1.635; 95%CI: 0.755-3.542, = 0.212) had no effect on mortality. Cardiopulmonary involvement and opportunistic infection were independent risk factors for mortality for SLE patients hospitalized for PIs. Use of high-dose pulse steroids and or immunosuppressants before hospitalization had no significant effects.
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http://dx.doi.org/10.3389/fmed.2021.732681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511406PMC
September 2021

Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort.

Front Immunol 2021 10;12:741369. Epub 2021 Sep 10.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objective: Although specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort.

Methods: A total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-β2-glycoprotein I (aβ2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits.

Results: Of the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aβ2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke.

Conclusion: Detection of aCL IgA, aβ2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice.
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http://dx.doi.org/10.3389/fimmu.2021.741369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461188PMC
September 2021

Quality of life in ambulatory pulmonary arterial hypertension in connective tissue diseases and its relationship with risk stratification.

Pulm Circ 2021 Jul-Sep;11(3):20458940211029899. Epub 2021 Jul 11.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

The Pulmonary Arterial Hypertension Symptoms and Impact Questionnaire (PAH-SYMPACT) is a PAH-specific patient-reported outcome scale assessing patients' quality of life from four aspects: cardiopulmonary symptoms, cardiovascular symptoms, physical impacts and cognitive/emotional impacts. This study aimed to validate the Chinese version of PAH-SYMPACT and explore its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). In addition, 75 patients with CTD-PAH confirmed by right heart catheterization were invited to complete questionnaires including PAH-SYMPACT, the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The demographic, clinical, laboratory and treatment data were collected. The endpoint was treatment goal achievement status in 6-12 months after completing the questionnaires, defined as an integrated outcome. Participants' mean age was 36.4 ± 11.9 years and the mean pulmonary arterial pressure was 38.9 ± 13.67 mmHg. The reliability of the PAH-SYMPACT domains ranged from 0.83 to 0.88. Results of factor analysis basically conformed the original PAH-SYMPACT. The treatment goal achievement (TGA) status in 6-12 months was significantly associated with physical impacts scores (odds ratio: 0.180, 95% confidence interval: 0.036-0.908, P=0.038). The Chinese version of PAH-SYMPACT is a reliable measurement to evaluate quality of life in CTD-PAH patients and is also a potential predictor of patient's condition change in routine clinical practice.
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http://dx.doi.org/10.1177/20458940211029899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278470PMC
July 2021

Comparison of Different Test Systems for the Detection of Antiphospholipid Antibodies in a Chinese Cohort.

Front Immunol 2021 2;12:648881. Epub 2021 Jul 2.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.

Background: Diagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China.

Methods: A total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and a2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features.

Results: CLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or a2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems.

Conclusion: CLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.
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http://dx.doi.org/10.3389/fimmu.2021.648881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283786PMC
September 2021

Platelet distribution width is highly associated with thrombotic events in primary antiphospholipid syndrome.

Clin Rheumatol 2021 Nov 2;40(11):4581-4588. Epub 2021 Jul 2.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Objective: Platelet activation is a possible pathogenic process contributing to thromboembolism in antiphospholipid syndrome (APS), and platelet distribution width (PDW) is associated with platelet activation. The objective of this study was to evaluate the association between platelet indices and thrombotic events in patients with primary APS.

Methods: This single-center cross-sectional study included 207 consecutive patients with APS treated at our institution between 2010 and 2019. Results of blood tests were recorded retrospectively from medical records.

Results: Of the included patients, 135 (65.2%) were female and 72 (34.8%) were male. They were classified into thrombotic (n = 150) or non-thrombotic (n = 57) groups. PDW, mean platelet volume, and large platelet ratio were significantly higher in the thrombotic group. In univariate logistic analysis, PDW was significantly associated with an increased odds of thrombosis [odds ratio (OR) 1.554, 95% confidence interval (CI) 1.289-1.873, p<0.001]. In multivariate logistic analysis, PDW and positive lupus anticoagulant (LA) were risk factors for thrombosis. Receiver operating characteristic analysis showed that PDW, combined with a positive LA, was a reliable indicator of thrombosis, with an area under the curve of 0.796 (95% CI 0.728-0.864). The optimal cutoff value for PDW was 12.4 fl, with a sensitivity of 72.0% and specificity of 77.2%. Multivariate logistic regression of PDW tertiles showed that the odds of thrombosis increased abruptly in the highest tertile.

Conclusion: This study confirmed the association between PDW and thrombotic events in APS patients, supporting the theory that platelet activation is a crucial mechanism of thrombosis in APS. Key Points • This study is the first to discuss the correlation between PDW and thromboses in patients with APS. • This study provides evidence of the important role of platelet activation in the pathogenesis of APS.
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http://dx.doi.org/10.1007/s10067-021-05843-zDOI Listing
November 2021

Myocardial involvement in idiopathic inflammatory myopathies: a multi-center cross-sectional study in the CRDC-MYO Registry.

Clin Rheumatol 2021 Nov 29;40(11):4597-4608. Epub 2021 Jun 29.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College &Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Objectives: This study aimed to investigate the associated factors of myocardial involvements (MIs) in patients with idiopathic inflammatory myopathies (IIMs).

Methods: In this multi-center cross-sectional study, 1946 patients with IIMs were enrolled from Chinese Rheumatism Data Center-Myositis Registry (CRDC-MYO). A total of 108 (5.5%) patients were identified with MIs, including congestive heart failure (n = 67, 62.0%), and severe arrhythmias (n = 61, 56.5%). The other 1838 IIM patients without IMs were set as the control group. Clinical features were collected including age, gender, comorbidities, clinical symptoms, clinical signs of both IIMs and MIs, lab findings including myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs), echocardiogram, and radiological exams. Multivariate logistic analysis was used to explore independent associated factors of MIs in patients with IIMs.

Results: Several independent associated factors were identified in multi-variate logistic regression, including positivity for anti-mitochondrial antibody-subtype 2 (AMA-M2) (OR 5.194, 95% CI 2.509-10.753, P < 0.001), elevation of creatine kinase (CK) (OR 2.611, 95% CI 1.312-5.198, P = 0.006), elevation of C-reactive protein (CRP) (OR 2.150, 95% CI 1.211-3.818, P = 0.001), and pulmonary hypertension (OR 4.165, 95% CI 1.765-9.882, P = 0.009). AMA-M2 and pulmonary hypertension were the most consistent associated factors in the polymyositis subgroup and the dermatomyositis/clinically amyopathic dermatomyositis subgroup.

Conclusions: MIs are rare but serious complication of IIMs could lead to congestive heart failure and severe arrhythmias. IIM patients with AMA-M2 positivity, elevation of CK and CRP, and pulmonary hypertension are more likely to develop MI complications. Key Points • This study investigated the independent associated factors for clinically significant myocardial involvements among idiopathic inflammatory myopathies in a large-scale, nation-wide multi-center cross-sectional study.
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http://dx.doi.org/10.1007/s10067-021-05828-yDOI Listing
November 2021

Prevalence and risk factors for left ventricular diastolic dysfunction in systemic sclerosis: a multi-center study of CRDC cohort in China.

Clin Rheumatol 2021 Nov 17;40(11):4589-4596. Epub 2021 Jun 17.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Objective: Left ventricular diastolic dysfunction (LVDD) is a common manifestation of cardiac involvement in systemic sclerosis (SSc), which is associated with increased mortality, but little is known about the risk factors. The aim is to determine the frequency and potential predictors of SSc-LVDD.

Methods: We conducted a prospective multi-center cohort study, enrolling 784 SSc patients assessed by echocardiography between April 2008 and June 2019. Diagnosis of systemic sclerosis was according to the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria. Data were compared between patients with and without LVDD, while univariate and multivariate regression analysis was performed to determine the factors independently associated with LVDD.

Results: LV diastolic dysfunction was present in 246/784 (31.4%) of the subjects. There were no significant differences in gender, BMI, or disease duration between the two groups. Around 40% of the patients in the SSc-LVDD group and in the SSc-non LVDD group had diffused cutaneous involvements. Factors independently associated with LV diastolic dysfunction in multivariable analysis included age at onset (OR 1.053, 95%CI 1.021-1.086, p = 0.001), pulmonary arterial hypertension (OR 3.057, 95%CI 1.468-6.367, p = 0.003), positivity of anti-RNP antibody (OR 2.455, 95%CI 1.049-5.745, p = 0.038), increased WBC count (OR 1.156, 95%CI 1.037-1.287, p = 0.009), elevated levels of uric acid (OR 1.003, 95%CI 1.000-1.006, p = 0.036), and triglyceride (OR 1.515, 95%CI 1.106-2.077, p = 0.010).

Conclusion: LV diastolic dysfunction was prevalent in the SSc population. Advanced onset age, PAH, positive anti-RNP antibody, increased WBC count, and adverse metabolic status were independent risk factors for SSc-related LVDD. Key Points • In this Chinese multi-center cohort of systemic sclerosis, LVDD is not a rare complication, with a prevalence of 31.4%. • The presence of advanced onset age, PAH, positive anti-RNP antibody, increased WBC count and adverse metabolic status were baseline predictors of developing LVDD in SSc.
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http://dx.doi.org/10.1007/s10067-021-05804-6DOI Listing
November 2021

Predicting the Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: A Chinese Systemic Lupus Erythematosus Treatment and Research Group Cohort Study.

Arthritis Rheumatol 2021 10 12;73(10):1847-1855. Epub 2021 Aug 12.

Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, and Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objective: Pulmonary arterial hypertension (PAH) is a life-threatening complication of systemic lupus erythematosus (SLE). However, there is no algorithm to identify those at high risk. This study was undertaken to develop a prediction model for PAH in patients with lupus that provides individualized risk estimates.

Methods: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed as having SLE. The diagnosis of PAH was confirmed by right-sided heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were performed for validation.

Results: Ninety-two lupus patients (2.54%) developed PAH during a median follow-up of 4.84 years (interquartile range 2.42-8.84). The final prediction model included 5 clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and 3 autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year PAH probability-predictive nomogram was established. The model was internally validated by Harrell's concordance index (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (>4.62%) lupus patients.

Conclusion: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of PAH in patients with SLE.
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http://dx.doi.org/10.1002/art.41740DOI Listing
October 2021

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study.

Lupus 2021 Aug 4;30(9):1459-1468. Epub 2021 Jun 4.

Department of Rheumatology and Immunology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients.

Methods: SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival.

Results: We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years,  = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years,  < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [ < 0.05], 57.6% [ < 0.05], and 16.5% [ < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE ( < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group ( < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28,  = 0.009).

Conclusions: ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.
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http://dx.doi.org/10.1177/09612033211021166DOI Listing
August 2021

Interventricular systolic asynchrony predicts prognosis in patients with systemic sclerosis-associated pulmonary arterial hypertension.

Rheumatology (Oxford) 2021 May 31. Epub 2021 May 31.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.

Objective: Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc) with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH.

Methods: Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV.

Results: Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (HR = 1.018, 95% CI 1.005-1.031, p = 0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, p = 0.002). Kaplan-Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank p = 0.001).

Conclusion: In conclusion, IVSA analyzed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.
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http://dx.doi.org/10.1093/rheumatology/keab465DOI Listing
May 2021

Applications of Protein Microarrays in Biomarker Discovery for Autoimmune Diseases.

Front Immunol 2021 3;12:645632. Epub 2021 May 3.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.

Dysregulated autoantibodies and cytokines were deemed to provide important cues for potential illnesses, such as various carcinomas and autoimmune diseases. Increasing biotechnological approaches have been applied to screen and identify the specific alterations of these biomolecules as distinctive biomarkers in diseases, especially autoimmune diseases. As a versatile and robust platform, protein microarray technology allows researchers to easily profile dysregulated autoantibodies and cytokines associated with autoimmune diseases using various biological specimens, mainly serum samples. Here, we summarize the applications of protein microarrays in biomarker discovery for autoimmune diseases. In addition, the key issues in the process of using this approach are presented for improving future studies.
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http://dx.doi.org/10.3389/fimmu.2021.645632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126629PMC
September 2021

Comparison of relapsing polychondritis patients with and without central nervous system involvement: A retrospective study of 181 patients.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211000547

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.

The relapsing polychondritis (RP) patients with central nervous system (CNS) involvement were rare. We aimed to determine the clinical characteristics of RP patients with CNS involvement. The clinical data of 181 RP patients, hospitalized at Peking Union Medical College Hospital between December 2005 and February 2019, were collected. The patients were categorized into two subgroups: 25 RP patients with CNS involvement, and 156 RP patients without CNS involvement. The involvement of the ear was more frequent in RP patients with CNS involvement, compared with those of RP patients without CNS involvement ( < 0.01). After controlling sex and the admission age, logistic regression analysis revealed hypertension (odds ratio = 4.308,  = 0.006) and involvement of eye (odds ratio = 5.158,  = 0.001) and heart (odds ratio = 3.216,  = 0.025) were correlated with RP patients with CNS involvement, respectively. In addition, pulmonary infection (odds ratio = 0.170,  = 0.020), tracheal involvement (odds ratio = 0.073,  < 0.01), and involvement of laryngeal (odds ratio = 0.034,  = 0.001), costochondral joint (odds ratio = 0.311,  = 0.013), sternoclavicular joint (odds ratio = 0.163,  = 0.017) and manubriosternal joint (odds ratio = 0.171,  = 0.021) were associated with RP patients without CNS involvement, respectively. In contrast to RP patients without CNS involvement, the incidence of ear involvement was higher in RP patients with CNS involvement. After controlling the potential confounding factor sex and the admission age, hypertension and involvement of eye and heart were related with RP patients with CNS involvement, respectively.
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http://dx.doi.org/10.1177/20587384211000547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995309PMC
November 2021

Validation of the REVEAL Prognostic Models in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.

Front Med (Lausanne) 2021 4;8:618486. Epub 2021 Mar 4.

Department of Epidemiology and Bio-Statistics, Institute of Basic Medical Sciences, China Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

No previous studies have investigated the predictive performance of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) prognostic equation and simplified risk score calculator in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). We aimed to validate these prediction tools in an external cohort of patients with SLE-PAH. In this study, the validation cohort consisted of patients with SLE-PAH registered in a prospective, multicenter, nationwide database between November 2006 and May2016. The follow-up of patients was censored at 1 year. Discrimination, calibration, model fit, and risk stratification of the REVEAL prognostic equation and simplified risk score calculator were validated. As a result, a total of 306 patients with SLE-PAH were included. The 1-year overall survival rate was 91.5%. The C-index of the prognostic equation was 0.736, demonstrating reasonably good discrimination, and it was greater than that for the simplified risk score calculator (0.710). The overall calibration slope was 0.83, and the Brier score was 0.079. The risk of renal insufficiency and World Health Organization Functional Class III (WHO FC III) were underestimated, and the risk assigned to a heart rate >92 bpm in the REVEAL prognostic models was not observed in our validation cohort. Both model discrimination and calibration were poor in the very high-risk group. In conclusion, the REVEAL models exhibit good discriminatory ability when predicting 1-year overall survival in patients with SLE-PAH. Findings from both models should be interpreted with caution in cases of renal insufficiency, WHO FC III, and heart rate >92 bpm.
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http://dx.doi.org/10.3389/fmed.2021.618486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969505PMC
March 2021

Renal Involvement and HBV Infection Are Common in Chinese Patients With Cryoglobulinemia.

Front Immunol 2021 25;12:580271. Epub 2021 Feb 25.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.

This study aimed to describe the main characteristics of Chinese patients with cryoglobulinemia, especially the characteristics of patients with different causes of cryoglobulinemia. Eighty inpatients diagnosed with cryoglobulinemia from different wards in Peking Union Medical College Hospital were included in this study. Demographic, clinical, biological, and renal pathological data were collected. We analyzed the characteristics of 61 patients with different causes of cryoglobulinemia. Most patients (36/80, 45%) were diagnosed between 40 and 60 years of age. The male: female ratio was 1:1.5. Mixed (II + III) cryoglobulinemia accounted for the majority (43.8%) of cases. Renal involvement (87.5%), cutaneous involvement (57.5%), and fever (27.5%) were the most common clinical manifestations, while other manifestations included serositis and pulmonary and gastrointestinal involvement. The most common renal histopathological pattern was membranoproliferative glomerulonephritis (25/42, 59.5%). The secondary causes of cryoglobulinemia included infectious diseases (26/61, 32.5%), such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and connective tissue diseases (22/61, 27.5%), such as lupus and hematologic tumors (13/61, 16.3%). Patients with hematologic tumors were diagnosed at an older age ( = 0.044) and mostly had type I cryoglobulinemia ( < 0.001). No significant difference in clinical or biological manifestations was found among patients with different causes of cryoglobulinemia. This is the largest cohort of Chinese patients with cryoglobulinemia. We found that renal involvement and HBV infection might be more common in Chinese patients with cryoglobulinemia.
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http://dx.doi.org/10.3389/fimmu.2021.580271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947000PMC
July 2021

Early Initiation of Anticoagulation Improves the Long-Term Prognosis in Patients With Antiphospholipid Syndrome Associated Portal Vein Thrombosis.

Front Med (Lausanne) 2021 4;8:630660. Epub 2021 Feb 4.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Portal vein thrombosis (PVT) is a rare and severe clinical phenotype of antiphospholipid syndrome (APS) with a poor prognosis. Anticoagulation therapy is efficient but is associated with potentially severe bleeding episodes, especially for those patients with thrombocytopenia. We conducted this case-control study to explore the clinical features and associated factors of PVT in APS patients, the re-canalization rate of the PVT after anticoagulation and investigate the beneficial effects of early initiation of anticoagulation in patients with APS associated PVT. We enrolled patients with APS associated PVT as the case group, and age-, and entry-time-matched APS patients without PVT (1:2) as the control group. We explored the associated factors of PVT in APS patients using multivariate logistic regression analysis. The re-canalization rate of the PVT after anticoagulation was analyzed using the survival analysis. A total of 34 patients (8 males and 26 females) with APS-PVT were enrolled, with a median follow-up time of 3 years (1.5, 7 years). Multivariate logistic regression analysis showed that thrombocytopenia (OR 6.4, 95%CI 1.561-26.218, = 0.01), hypersensitive c-reactive protein >3 mg/L (OR 4.57, 95%CI 1.426-14.666, = 0.011), anti β2GPI positive (OR 5, 95%CI 1.816-13.772, = 0.002) and aPL double-positive (OR 4.08, 95%CI 1.312-12.429, = 0.013) were independent associated factors for PVT in APS. Survival analysis revealed that effective anticoagulation could increase re-canalization rate significantly (log-rank = 0.001), with better prognosis (lower mortality rate, log-rank = 0.045). PVT could be the first presentation of APS with insidious onset and atypical clinical symptoms and easily be misdiagnosed. For patients with APS, double aPLs positive, thrombocytopenia, and inflammation could be the associated factors of PVT. Early diagnosis and anticoagulation treatment can bring thrombus re-canalization thereby significantly improving the prognosis.
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http://dx.doi.org/10.3389/fmed.2021.630660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890015PMC
February 2021

MicroRNA-320a: an important regulator in the fibrotic process in interstitial lung disease of systemic sclerosis.

Arthritis Res Ther 2021 01 11;23(1):21. Epub 2021 Jan 11.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Background: Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD.

Methods: miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics.

Results: miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-β stimulation, the expression of miR-320a and collagen genes were significantly upregulated.

Conclusion: miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.
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http://dx.doi.org/10.1186/s13075-020-02411-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802184PMC
January 2021

Chinese SLE Treatment and Research Group Registry (CSTAR) XIII: prevalence and risk factors for chronic scarring alopecia in patients with systemic lupus erythematosus.

Arthritis Res Ther 2021 01 11;23(1):20. Epub 2021 Jan 11.

Department of Rheumatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.

Background: Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case-control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients.

Methods: SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements, and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia.

Results: We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p < 0.001), high SLICC/ACR-DI (OR 1.409, p < 0.001), and positive anti-Sm (OR 1.374, p = 0.029) were risk factors for scarring alopecia, while renal (OR 0.714, p = 0.028) and cardio-respiratory involvements (OR 0.347, p = 0.044), and immunosuppressant treatment (OR 0.675, p < 0.001) were significantly negative associated with it.

Conclusions: The prevalence of scarring alopecia in SLE patients is 7.80%. Active treatment strategies should be adopted to prevent scarring alopecia occurring.
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http://dx.doi.org/10.1186/s13075-020-02407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802218PMC
January 2021

Factors Associated With Renal Involvement in Primary Sjögren's Syndrome: A Meta-Analysis.

Front Med (Lausanne) 2020 26;7:614482. Epub 2020 Nov 26.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Renal impairment is a critical complication in primary Sjögren's syndrome (pSS), resulting in chronic renal disease and even death. This meta-analysis was designed to find out the relevant factors of renal involvement in pSS. PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were systemically searched until August 30, 2019. Studies were selected according to inclusion criteria, and data was extracted by two researchers independently. The Newcastle-Ottawa Scale was applied for quality assessment. Random- and fixed-effects models were used in this meta-analysis based on the result of the heterogeneity test. Meanwhile, a sensitivity analysis was conducted to investigate the cause of heterogeneity. Publication bias was shown in the funnel plot and evaluated further by Begg's and Egger's tests. Of the 9,989 articles identified, five articles enrolling 1,867 pSS patients were included in the final analysis, 533 with and 1,334 without renal involvement. There was no statistical significance in age and gender between these two groups. According to the meta-analysis, anti-SSB antibody, and arthralgia showed a significant association with renal involvement in pSS, the overall odds ratio (OR) values of which were 1.51 (95% CI, 1.16-1.95) and 0.59 (95% CI, 0.46-0.74), respectively. On the other hand, the overall OR values of anti-SSA antibody, rheumatoid factor, dry eyes, and labial salivary gland biopsy were just 0.90 (95% CI, 0.49-1.64), 1.05 (95% CI, 0.59-1.86), 0.60 (95% CI, 0.34-1.06), and 1.38 (95% CI, 0.98-1.95), respectively. The presence of anti-SSB antibody is positively associated with renal involvement in pSS, while arthralgia is inversely associated. Large-scale prospective cohort studies are needed in the future to identify further risk factors.
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http://dx.doi.org/10.3389/fmed.2020.614482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726424PMC
November 2020

Association between acute phase reactants, interleukin-6, tumor necrosis factor-α, and disease activity in Takayasu's arteritis patients.

Arthritis Res Ther 2020 12 10;22(1):285. Epub 2020 Dec 10.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.

Background: To investigate the association between blood biomarkers and disease activity of Takayasu's arteritis (TAK) in a follow-up cohort.

Methods: Disease activity was assessed by clinical manifestations and repeated vascular Doppler examinations. The association between erythrocyte sedimentation rate (ESR), serum levels of high-sensitive C-reactive protein (hsCRP), interleukin-6(IL-6), and tumor necrosis factor-α (TNFα) and disease activity were analyzed by logistic regression and survival analysis. Kaplan-Meier method was used to estimate the cumulative remission rate curve, log-rank tests for group comparison, and Cox regression for estimating hazard ratios of these parameters for disease activity.

Results: 428 patients were included. 188 patients were in active disease, and 240 patients were in inactive disease at baseline. Elevation of ESR, hsCRP, and IL-6 were associated with active disease at baseline and during follow-up. Cox regression and Kaplan-Meier analysis showed that lower possibility and longer time to remission were associated with elevated ESR (hazard ratio [HR] = 0.32, 80 vs 33 weeks, p < 0.001), hsCRP (HR = 0.45, 70 vs 31 weeks, p < 0.001), and IL-6 (HR = 0.54, 66 vs 34 weeks, p < 0.01) in patients with active disease at baseline, while higher risk and shorter time for relapse were associated with elevated ESR (HR = 2.1, 59 vs 111 weeks, p < 0.001), hsCRP (HR = 2.1, 79 vs 113 weeks, p < 0.001), IL-6 (HR = 2.5, 64 vs 117 weeks, p < 0.001), and TNFα (HR = 2.7, 65 vs 114 weeks, p < 0.001) in patients with inactive disease at baseline.

Conclusions: Elevated ESR, CRP, and IL-6 are associated with active disease, lower possibility, and longer time to achieve disease remission. Elevation of any among ESR, CRP, IL-6, and TNFα is associated with high risk and short time for relapse during follow-up.
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http://dx.doi.org/10.1186/s13075-020-02365-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726865PMC
December 2020

The long-term prognosis of pneumomediastinum associated with dermatomyositis: a two-centre retrospective cohort study.

Rheumatology (Oxford) 2021 05;60(5):2288-2295

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: Pneumomediastinum (PnM) is a rare but life-threatening complication of DM. The present study aims to characterize the long-term prognosis and prognostic factors of DM-associated PnM.

Methods: Inpatients with DM-associated PnM were retrospectively enrolled from two tertiary referral centres for rheumatic disease. The enrolled patients were divided into survivors or non-survivors. Information about the demographics, clinical manifestations, CT scan features, laboratory findings and outcomes were collected from their medical records. A least absolute shrinkage and selection operator regularized Cox regression model was used to select the most relevant factors. Prognosis was analysed using a Kaplan-Meier curve. A Cox proportional hazards model was used to identify independent predictive factors for long-term survival.

Results: A total of 62 patients (26 women) with DM-associated PnM were enrolled. The mean age was 44.3 years (s.d. 11.7). The median follow-up duration was 17 days (quartiles 7, 266.5). Thirty-five patients died during follow-up. The survival rates were 75.4% at 1 week, 46.2% at 3 months and 41.9% at 1 year. The Cox proportional hazards model identified the development of fever [hazard ratio (HR) 3.23 (95% CI 1.25, 8.35), P = 0.02] and a decrease in the number of lymphocytes [HR 2.19 (95% CI 1.10, 4.39), P = 0.03] as independent risk factors for death.

Conclusion: The results suggest poor overall survival among patients with DM-associated PnM. Survival during the first 3 months is crucial for long-term survival. Meanwhile, the development of fever and a decrease in the number of lymphocytes were associated with long-term mortality. Early recognition and prompt treatment of this high-risk group of DM patients is therefore important.
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http://dx.doi.org/10.1093/rheumatology/keaa582DOI Listing
May 2021

CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases.

bioRxiv 2020 Nov 10. Epub 2020 Nov 10.

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.
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http://dx.doi.org/10.1101/2020.11.10.376277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668730PMC
November 2020

Relationship between disease activity, organ damage and health-related quality of life in patients with systemic lupus erythematosus: A systemic review and meta-analysis.

Autoimmun Rev 2021 Jan 22;20(1):102691. Epub 2020 Oct 22.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China. Electronic address:

Objectives: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease that may lead to considerable physical, psychological, and socioeconomical burden. In previous studies, inconsistent results were reported for the association of disease activity and organ damage with health-related quality of life (HRQoL). This paper aimed to explore the relationship between disease activity, organ damage, and HRQoL measured by SF-36, EQ-5D, LupusQoL, and LupusPRO and investigate whether the correlation is region-specific.

Methods: We systematically searched for studies reporting the association between SLE disease activity, organ damage, and HRQoL in MEDLINE, EMBASE, PsycINFO, World of Science, the Cochrane Library, and CINAHL from inception to December 2019. A meta-analysis and region subgroup analysis were performed with a random-effects model to estimate pooled correlation coefficients and heterogeneity.

Results: Forty articles were included representing of 6079 adult SLE patients. The meta-analysis of SF-36 and LupusPRO studies revealed mild to moderate negative correlations between disease activity and domains of these HRQoL measurements (correlation coefficient r ranging from -0.27 to -0.07). Likewise, negative correlations were found between organ damage and domains of SF-36 and LupusPRO (r ranging from -0.25 to -0.08). The pooled correlation coefficient is relatively higher in physical functioning related domains than mental health. In the region subgroup analysis, disease activity had strong negative correlations with SF-36 domains in African and European SLE patients, while organ damage had the strongest negative correlation with SF-36 domains in Asian SLE patients (p < 0.010).

Conclusion: This study provides the first comprehensive assessment of the relationship between disease activity, organ damage, and four popular HRQoL instruments, which provides useful insight into the target therapy in SLE management.
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http://dx.doi.org/10.1016/j.autrev.2020.102691DOI Listing
January 2021

Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population.

Front Immunol 2020 5;11:568503. Epub 2020 Oct 5.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.

Objective: Antiphospholipid syndrome (APS) is characterized by the presence of anti-phospholipid (aPL) antibodies. However, the relationship between the immunoglobulin (Ig) A isotype of aPL positivity and its clinical utility in APS diagnosis is controversial. Presently, we determine the clinical utility of IgA-aPL from consecutive patients in a large cohort from the Chinese population and patients with APS whose aPL profiles were obtained.

Methods: The detection of anticardiolipin (aCL) and anti-β glycoprotein-Ⅰ (aβGPⅠ) antibodies of the IgA/IgG/IgM isotype by paramagnetic particle chemiluminescent immunoassay was carried out in sera from 7293 subjects. 153 primary APS (PAPS) patients and 59 patients with secondary APS (SAPS) were included in this study.

Results: In total, 1,082 out of 7,293 (2.55%) subjects had a positive IgA-aPL test, and the prevalence of isolated IgA-aPL was 0.29% (21/7,293) in the general population. The prevalence of IgA-aPL in the PAPS patients was 12.42% (19/153); however, only one patient (0.65%) presented with isolated IgA-aPL. Fifty (25.9%) of the SAPS had IgA-aPL, none of whom lacked IgG/IgM-aPL. The combination of the IgA isotype and the IgG/IgM isotype did not increase the diagnostic performance when compared with the IgG/IgM isotype of aCL or aβGPⅠ, respectively. IgA-aPL was not associated with clinical manifestation in patients with APS.

Conclusion: Isolated IgA-aPL is rare in the general population as well as in patients with APS. Whether in the laboratory or in clinical practice, the presence of IgA-aPL does not provide added value for the diagnosis of APS in the Chinese population.
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http://dx.doi.org/10.3389/fimmu.2020.568503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573363PMC
May 2021

Aberrant expression of cell-free nucleosomes in dermatomyositis/polymyositis.

Dermatol Ther 2020 11 10;33(6):e14460. Epub 2020 Nov 10.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Nucleosomes are typically located intracellularly, and extracellular levels of nucleosomes indicated the degree of cell death. We postulated aberrant nucleosomes expression in dermatomyositis (DM) and polymyositis (PM). To assess the aberrant expression of circulating nucleosomes in DM and polymyositis. 76 consecutive DM and PM patients from 1 September 2017 to 31 October 2018 were enrolled in this study, in addition to 20 healthy controls. The levels of circulating nucleosomes, with 16 kinds of detectable myositis-specific antibodies (MSAs) were detected in IIMs patients using enzyme-linked immunosorbent assay kit (ELISA). Receiver operating characteristic (ROC) curve analysis was performed for evaluating the ability of this candidate marker for detecting DM/PM. The results showed that the levels of circulating nucleosomes in DM/PM patients were significantly higher than that in normal individuals. Specifically, elevated levels of nucleosomes were associated with MDA5 Ab, ARS, and TIF1γAb. In addition, elevated levels of circulating nucleosomes correlated with skin eruption. This study has evidenced nucleosomes as a potential new biomarker of DM/PM. Aberrant nucleosomes expression occurs in myositis patients and the difference in nucleosomes expression between patients with and without skin eruption is statistically significant. A unique expression profile of elevated serum nucleosomes was detected in DM/PM-MDA5 Ab(+), ASS, and TIF1γAb(+).
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http://dx.doi.org/10.1111/dth.14460DOI Listing
November 2020

Clinical characteristics and prognosis of concomitant systemic lupus erythematosus and primary biliary cholangitis.

Clin Rheumatol 2021 May 16;40(5):1819-1826. Epub 2020 Oct 16.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.

Objective: This study aimed to identify the clinical characteristics of systemic lupus erythematosus-primary biliary cholangitis (SLE-PBC) patients and to compare the manifestations and prognosis with systemic lupus erythematosus (SLE) patients.

Methods: Twenty-one inpatients with concomitant SLE and primary biliary cholangitis (PBC) were identified in our hospital. Baseline clinical manifestations, laboratory results, disease activity, and organ damage, as well as changes in disease manifestations and therapies, were retrospectively analyzed. Baseline clinical characteristics, survival rate, and flare-ups were compared with 254 SLE patients also from our hospital.

Results: The prevalence of concomitant PBC in SLE inpatients was 0.27%. Over half of the patients were diagnosed with SLE and PBC simultaneously. Compared with SLE patients, SLE-PBC patients started the symptom of SLE at an older age, with a longer delay before the diagnosis of SLE (P < 0.05). Hematological and muscular involvement, pulmonary arterial hypertension, and interstitial lung disease were more common in SLE-PBC patients (P < 0.05). Kaplan-Meier estimate showed a significantly lower survival rate in SLE-PBC group, with 3-year survival rate at 88.4%.

Conclusion: Concomitant PBC might have a negative impact on the survival of SLE, with older age at SLE onset, longer delay before SLE diagnosis, and higher baseline damage. More intensive therapy and prevention of hepatic toxicity need to be considered. Key Points • Hematological and muscular involvement, PAH, and ILD were more common in SLE PBC than in SLE. • The study firstly reported the survival rate of SLE PBC patients. • More intensive therapy and prevention of hepatic toxicity are needed for SLE-PBC.
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http://dx.doi.org/10.1007/s10067-020-05457-xDOI Listing
May 2021

Superficial Siderosis and Microbleed Restricted in Cortex Might Be Correlated to Atrophy and Cognitive Decline in Sneddon's Syndrome.

Front Neurol 2020 16;11:1035. Epub 2020 Sep 16.

Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Sneddon's syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent transient ischemic attack or ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued. We aimed to investigate the hemorrhagic imaging features of Sneddon's syndrome and explore the possible mechanism and clinical relevance. Clinical data and cerebral MR imaging including T2 sequence of seven consecutive patients with Sneddon's syndrome were reviewed. The most common neurological manifestations were cognitive impairment and stroke attack (71.4%), followed by seizures and movement disorder (28.6%). Cerebral microbleeds were detected in six patients on T2 sequence, all of them presented with cortical microbleeds, only one of them with microbleeds in basal ganglion. More than five microbleeds were observed in four of these six patients. The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified mainly involving cortical watersheds in five cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in one patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients. This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon's syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome.
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http://dx.doi.org/10.3389/fneur.2020.01035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525095PMC
September 2020

Prevalence, predictors and prognostic benefits of remission achievement in patients with systemic lupus erythematosus: a systematic review.

Arthritis Care Res (Hoboken) 2020 Sep 28. Epub 2020 Sep 28.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: To systematically review and evaluate the prevalence, potential predictors and prognostic benefits of remission achievement in patients with systemic lupus erythematosus (SLE).

Methods: Studies reporting prevalence, predictors and prognostic benefits of remission in adult SLE patients were searched and selected from Pubmed and EMBASE databases. Studies were reviewed for relevance and quality. Two reviewers independently assessed studies and extracted data.

Results: Data from forty-one studies including 17270 patients were included and analyzed. Although no consensus has been achieved on the definition of remission, clinical disease activity, serological activity, duration and treatment are agreed to be critical components of defining remission status. In most studies published in the recent 5 years, 42.4% to 88% patients achieved and maintained the remission status for one year, and 21.1% to 70% for at least 5 years. Factors associated with remission included older age at diagnosis, lower baseline disease activity and absence of major organ involvement, while positive serological results were shown to be negatively associated with remission. Remission-especially prolonged remission-when achieved, demonstrated an association with lower accrual of damage and better quality of life among patients with SLE.

Conclusions: Remission is an achievable and desirable target for SLE patients, proven to be associated with prognostic benefits. Further development and assessment of a clear remission definition, a risk stratification model as well as a full algorithm with frequency of monitoring, timepoints for treatment adjustment and drug withdrawal are required.
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http://dx.doi.org/10.1002/acr.24464DOI Listing
September 2020

Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis.

Ther Adv Musculoskelet Dis 2020 14;12:1759720X20953336. Epub 2020 Sep 14.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan, Beijing 100730, China.

Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients.

Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE.

Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 4.0 ± 3.4,  = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day 5.9 ± 4.0 mg/day,  = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l 0.884 ± 0.219 g/l,  < 0.001; complement 4: 0.105 ± 0.059 g/l 0.141 ± 0.069 g/l,  < 0.001; anti-dsDNA antibody, 200 ± 178 IU/ml 156 ± 163 IU/ml,  = 0.022]. The remission proportions of arthritis, skin rash, and thrombocytopenia were 100%, 88.8%, and 46.2%, respectively. A total of 41.2% of lupus nephritis (LN) patients achieved renal remission, but the average 24-h urine protein level was not significantly changed. Meta-analysis enrolled five studies with 149 patients included, and revealed similar results regarding the changes of SLEDAI-2K [-3.5 (-5.0, -2.1)], C3 [0.224 (0.136, 0.311) g/l] and daily dosage of prednisone [-12.7 (-19.9, -5.6) mg/day].

Conclusion: Sirolimus might be effective and tolerated in SLE. The role of sirolimus in LN requires further study.
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http://dx.doi.org/10.1177/1759720X20953336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493251PMC
September 2020
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