Publications by authors named "Miaojia Zhang"

74 Publications

Correlation of peripheral CD4+GranzB+CTLs with disease severity in patients with primary Sjögren's syndrome.

Arthritis Res Ther 2021 Oct 12;23(1):257. Epub 2021 Oct 12.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Introduction: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS.

Methods: We recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland.

Results: The percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently (p < 0.05), and they are the risk factor of extraglandular involvement (odds ratio = 1.928). Moreover, they could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS and 0.851 to presume extraglandular manifestations. The best diagnostic cutoff point was 4.865 for pSS patients.

Conclusion: In this study, we provide new evidence indicating the involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.
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http://dx.doi.org/10.1186/s13075-021-02632-6DOI Listing
October 2021

Upregulated IL-10 induced by E2F2-miR-17-5p circuitry in extrafollicular effector B cells contributes to autoantibody production in systemic lupus erythematosus.

Arthritis Rheumatol 2021 Sep 27. Epub 2021 Sep 27.

Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Objective: Elevated interleukin 10 (IL10) in SLE patients has B-cell promoting effects, contributing to autoantibody production and tissue damage. We aimed to characterize upregulated IL10 B-cell subsets and dysregulated IL10 expression in SLE B cells for new therapeutic options.

Methods: Proportions of Th10 and IL10 B-cell subsets in PBMCs were assessed using flow cytometry. The IL10-3'UTR dual-luciferase vector was constructed and co-transfected with siRNA, miRNA mimics or inhibitors into RAJI cell line. Transcript levels were quantified using Taqman assays.

Results: Culture conditions that induced IL10 Breg in healthy controls (HC) resulted in expansion of IL10 DN2 (IgD CD27 CD21 CD11c ) B-cells in SLE PBMCs. Proportions of IL10 DN2, but not those of IL10 DN2, correlated with disease activity, levels of antibodies to dsDNA, and associated with high levels or seropositivity of anti-Smith and anti-cardiolipin IgG in SLE patients from two cohorts of mainly African Americans and Asians, respectively. Proportions of Th10 (CD45RA CXCR5 CXCR3 PD1 CD4 ) cells correlated with IL10 DN2 frequencies, ANA titers and proteinuria levels in SLE patients. Screening predicted IL10 3'UTR-targeting miRNAs in SLE B cells identified miR-17-5p and miR-20a-5p with their levels inversely correlated with IL10 and transcription factor E2F2. In RAJI cells, knockdown of E2F2 expression resulted in increased levels of miR-17-5p and miR-20a-5p and decreased IL10 mRNA and protein levels, and overexpression and inhibition of miR-17-5p down-regulated and up-regulated IL10 mRNA levels respectively; suggesting regulation of IL10 expression by E2F2-miR-17-5p loop.

Conclusion: IL10 promotes extrafollicular autoimmune responses in active SLE patients, which might be dampened by targeting the E2F2-miR-17-5p circuitry.
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http://dx.doi.org/10.1002/art.41987DOI Listing
September 2021

Human SLE variant -R90H promotes kidney damage and murine lupus through enhanced Tfh2 responses induced by defective efferocytosis of macrophages.

Ann Rheum Dis 2021 Sep 23. Epub 2021 Sep 23.

Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA

Objectives: We previously identified a hypomorphic variant, p.Arg90His (p.R90H) of neutrophil cytosolic factor 1 ( a regulatory subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 complex), as an putative causal variant for systemic lupus erythematosus (SLE), and established a knock-in (KI) H90 variant in the C57BL/6 background to study how this variant promotes lupus development.

Methods: Wild type (WT) and KI littermates were assessed for immune profiles and lupus-like features. Disease activity and renal damage of patients with SLE were assessed by systemic lupus erythematosus disease activity index (SLEDAI) and renal items of systemic lupus international collaborating clinics (SLICC), respectively.

Results: Compared with WT littermates, 5-week-old homozygous KI mice had reduced oxidative burst, splenomegaly, elevated type I interferon (IFN-I) scores, increased ratios of splenic follicular T helper 2 (Tfh2) to either T follicular regulatory (Tfr) or Tfh1 cells, increased ANA follicular, germinal centre and plasma cells without spontaneous kidney disease up to 1 year of age. Pristane treatment exacerbated the immune dysregulation and induced IFN-I-dependent kidney disease in 36-week-old H90 KI female mice. Decreased efferocytosis of macrophages derived from KI mice and patients with homozygous H90 SLE promoted elevated ratios of Tfh2/Tfr and Tfh2/Tfh1 as well as dysregulated humoral responses due to reduced voltage-gated proton channel 1 (Hv1)-dependent acidification of phagosome pH to neutralise the decreased electrogenic effect of the H90 variant, resulting in impaired maturation and phagosome proteolysis, and increased autoantibody production and kidney damage in mice and patients with SLE of multiple ancestries.

Conclusions: A lupus causal variant, NCF1-H90, reduces macrophage efferocytosis, enhances Tfh2 responses and promotes autoantibody production and kidney damage in both mice and patients with SLE.
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http://dx.doi.org/10.1136/annrheumdis-2021-220793DOI Listing
September 2021

The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.

Sci Rep 2021 09 20;11(1):18591. Epub 2021 Sep 20.

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.
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http://dx.doi.org/10.1038/s41598-021-98111-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452734PMC
September 2021

Blockade of adiponectin receptor 1 signaling inhibits synovial inflammation and alleviates joint damage in collagen-induced arthritis.

Clin Rheumatol 2021 Aug 13. Epub 2021 Aug 13.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Objectives: Adiponectin (AD) highly expressed in synovial tissue correlates closely with progressive bone erosion in rheumatoid arthritis (RA). However, it remains unknown whether AD receptor mediates the pathogenesis of RA. This study aimed to investigate the effects of adiponectin receptor 1 (AdipoR1) signaling on synovial inflammation and joint damage in collagen-induced arthritis.

Methods: AD and AdipoR1 expression in synovial tissue of RA and osteoarthritis (OA) patients were tested by PCR and western blotting. The frequency of AdipoR1 on RA synovial fibroblasts (RASFs) was examined by flow cytometry after stimulation with AD, IL-6, or TNF-α. AdipoR1 was knocked down in human RASF cell line (MH7A) and CIA mice joints using lentiviral particles carrying the AdipoR1 short hairpin RNA (shAdipoR1). Both the proliferation and apoptosis of MH7A and the secretion of inflammatory factors from MH7A were examined in vitro. The therapeutic effect of local AdipoR1 inhibition on CIA mice was assessed in vivo.

Results: Both the expression of AD and AdipoR1 were significantly higher in RA synovial tissue. AdipoR1 on RASFs was upregulated by AD. Silencing AdipoR1 remarkably reduced lipopolysaccharides-induced proliferation and promoted the apoptosis of MH7A. Moreover, AdipoR1 knockdown inhibited the release of inflammatory factors in vitro. In CIA mice, local AdipoR1 inhibition effectively decreased joint inflammation and alleviated bone destruction via suppressing RANKL and RANKL/OPG ratio in vivo.

Conclusions: AdipoR1 signaling participates in the process of synovial inflammation and joint damage in CIA. Local blockade of AdipoR1 might be a new target for the clinical treatment of RA. Key points • Local AdipoR1 inhibition decreased joint inflammation and alleviated bone destruction in CIA.
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http://dx.doi.org/10.1007/s10067-021-05846-wDOI Listing
August 2021

Adiponectin Enhances B-Cell Proliferation and Differentiation Activation of Akt1/STAT3 and Exacerbates Collagen-Induced Arthritis.

Front Immunol 2021 18;12:626310. Epub 2021 Mar 18.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Although B cells have been shown to contribute to the pathogenesis of rheumatoid arthritis (RA), the precise role of B cells in RA needs to be explored further. Our previous studies have revealed that adiponectin (AD) is expressed at high levels in inflamed synovial joint tissues, and its expression is closely correlated with progressive bone erosion in patients with RA. In this study, we investigated the possible role of AD in B cell proliferation and differentiation. We found that AD stimulation could induce B cell proliferation and differentiation in cell culture. Notably, local intraarticular injection of AD promoted B cell expansion in joint tissues and exacerbated arthritis in mice with collagen-induced arthritis (CIA). Mechanistically, AD induced the activation of PI3K/Akt1 and STAT3 and promoted the proliferation and differentiation of B cells. Moreover, STAT3 bound to the promoter of the Blimp-1 gene, upregulated Blimp-1 expression at the transcriptional level, and promoted B cell differentiation. Collectively, we observed that AD exacerbated CIA by enhancing B cell proliferation and differentiation mediated by the PI3K/Akt1/STAT3 axis.
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http://dx.doi.org/10.3389/fimmu.2021.626310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012765PMC
September 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

Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Environ Res 2021 04 13;195:110875. Epub 2021 Feb 13.

Department of Rheumatology and Immunology, Changzheng Hospital, The Second Military Medical University, Shanghai, China; School of Clinical Medicine, Tsinghua University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China. Electronic address:

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 μm (PM), sulfur dioxide (SO), nitrogen dioxide (NO), carbon monoxide (CO), and ozone (O). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM and NO were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM and NO, respectively. This positive association between LN and NO was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O was not generally associated with LN. Finally, the negative associations of LN with SO were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.
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http://dx.doi.org/10.1016/j.envres.2021.110875DOI Listing
April 2021

Creatinine clearance rate predicts prognosis of patients with systemic lupus erythematosus: a large retrospective cohort study.

Clin Rheumatol 2021 Jun 5;40(6):2221-2231. Epub 2020 Nov 5.

Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, China.

Objective: To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR).

Methods: We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI).

Results: Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59-3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02-3.19) and 6.84 (3.05-15.36).

Conclusions: A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival. Key points • Decreasing creatinine clearance rate (Ccr) was positively associated with an overall mortality of SLE patients, with a dose-response relationship. • Moreover, decreasing Ccr was associated with elevated mortality primarily due to infection and renal failure.
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http://dx.doi.org/10.1007/s10067-020-05485-7DOI Listing
June 2021

Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus.

Rheumatology (Oxford) 2021 04;60(4):1774-1783

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Objective: To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients.

Methods: Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI.

Results: We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements.

Conclusion: Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.
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http://dx.doi.org/10.1093/rheumatology/keaa485DOI Listing
April 2021

Serum uric acid is associated with disease severity and may predict clinical outcome in patients of pulmonary arterial hypertension secondary to connective tissue disease in Chinese: a single-center retrospective study.

BMC Pulm Med 2020 Oct 19;20(1):272. Epub 2020 Oct 19.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Previous studies have shown that serum uric acid (UA) levels are correlated with the severity of idiopathic pulmonary arterial hypertension (IPAH) and are predictors of disease prognosis. Still, few studies have explored the value of serum UA in pulmonary arterial hypertension secondary to connective tissue disease (CTD-PAH). This retrospective study aimed to investigate the clinical value of serum UA levels in patients with CTD-PAH.

Methods: Fifty CTD-PAH patients were enrolled in our study, from which baseline UA levels, respective variations, and additional clinical data were collected. The potential association between baseline UA level and severity of CTD-PAH was investigated. Furthermore, the relationship between baseline UA and survival rate of CTD-PAH patients, as well as between UA variations and survival rate of pulmonary hypertension secondary to connective tissue disease (CTD-PH) patients was discussed.

Results: Baseline serum UA levels were positively correlated with pulmonary vascular resistance (PVR). During the follow-up period, 3 CTD-PAH and 12 CTD-PH patients died. Kaplan-Meier survival curves showed lower survival rate in patients with hyperuricemia than in patients with normouricemia, in both groups (CTD-PAH group p = 0.041, CTD-PH group p = 0.013). Concerning serum UA variations, patients with persistent hyperuricemia showed the lowest survival rate when compared with patients with steady normouricemia (p = 0.01) or patients with decresing serum UA levels, i.e. undergoing from a status of hyperuricemia to a status of normouricemia (p = 0.023).

Conclusion: Baseline serum UA levels might predict severity of CTD-PAH. Together with baseline values, changes of uric acid level may predict the clinical prognosis of the disease.
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http://dx.doi.org/10.1186/s12890-020-01309-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574226PMC
October 2020

Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis.

Front Immunol 2020 18;11:2040. Epub 2020 Aug 18.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the role of AdipoR1 in Th17 differentiation. RNA-sequencing (RNA-seq) demonstrated that knockout reduced the expression of a variety of T cell related genes, with showing the greatest level of down-regulation. AdipoR1 deficiency inhibited Th17 cell differentiation and ameliorated joint inflammation in antigen-induced arthritis mice. Moreover, AdipoR1-deficent CD4T cells displayed reduced Hypoxia-Inducible Factor-1α expression leading to glycolysis inhibition during naïve CD4T cell differentiation into Th17 cells. We describe a novel function of AdipoR1 in regulating Th17 cell differentiation through modulating HIF-1α-dependent glycolysis.
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http://dx.doi.org/10.3389/fimmu.2020.02040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461876PMC
April 2021

Clinical analysis of macrophage activation syndrome in adult rheumatic disease: A multicenter retrospective study.

Int J Rheum Dis 2020 Nov 3;23(11):1488-1496. Epub 2020 Sep 3.

Department of Rheumatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Aim: To evaluate the clinical and laboratory characteristics, prognostic factors, and outcome of adult rheumatic disease-associated macrophage activation syndrome (MAS).

Method: A multicenter retrospective study was performed across 4 tertiary hospitals in China between January 1, 2017 to December 31, 2019.

Results: There were 61 rheumatic disease patients with MAS enrolled into this retrospective clinical study. Fever and hyperferritinemia are the most frequent clinical feature and laboratory abnormality in MAS patients. Serum ferritin > 6000 ng/mL (odds ratio [OR] = 9.46, 95% CI = 2.53-47.13, P = .005) and hemophagocytosis in bone marrow smear (OR = 11.12, 95%, CI = 3.29-50.65, P = .001) were the 2 most prominent predictive factors indicating MAS occurrence. The 90-day all-cause mortality rate of all rheumatic disease patients with MAS was 22.9% (hazards ratio [HR] = 2.15, 95% CI = 0.81-6.78, P = .05). Platelets < 100 × 10 /L (HR = 3.23, 95% CI = 2.51-4.81, P = .01) and ferritin > 6000ng/mL (HR = 6.12, 95% CI = 2.93-16.27, P = .005) were independent predictors of poor outcome in rheumatic disease-associated MAS.

Conclusion: Macrophage activation syndrome could be a fatal complication in rheumatic disease. Patients presenting with unexplained fever, serum ferritin > 6000 ng/mL, hepatosplenomegaly and cytopenia at baseline should raise the suspicion of MAS. The presence of serum ferritin > 6000 ng/mL, hepatosplenomegaly and low number of platelets was associated with poor outcome.
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http://dx.doi.org/10.1111/1756-185X.13955DOI Listing
November 2020

MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Aging (Albany NY) 2020 07 17;12(14):14376-14390. Epub 2020 Jul 17.

Division of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China.

Fibroblast-like synoviocytes (FLSs) are key effector cells in the pathogenesis of rheumatoid arthritis (RA) and display a unique aggressive tumor-like phenotype with remarkable hyperplasia, increased cell migration and invasion. How FLSs undergo these changes in RA remains unknown. We previously reported a novel function of transcription factor SOX5 in RA-FLSs that promote cell migration and invasion. In this study, we found that miR-15a/16 directly targets the 3'UTR and suppresses expression. Moreover, miR-15a/16 is significantly down-regulated in RA-FLSs, which negatively correlates with expression. Transfection with miR-15a/16 mimics in RA-FLSs inhibits cell migration, invasion, and expression. Overexpression in RA-FLSs decreases miR-15a/16 expression and rescues miR-15a/16-mediated inhibitory effect. Furthermore, RA patients with the lower baseline serum miR-15a/16 level present poor response of 3 months disease-modifying antirheumatic drugs (DMARDs) therapy. Collectively, this study reveals that miR-15a/16/SOX5 axis functions as a key driver of RA-FLSs invasion, migration and inflammatory response in a mutual negative feedback loop and correlates with DMARDs treatment response in RA.
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http://dx.doi.org/10.18632/aging.103480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425471PMC
July 2020

Pulmonary arterial hypertension associated with primary Sjögren's syndrome: a multicentre cohort study from China.

Eur Respir J 2020 11 19;56(5). Epub 2020 Nov 19.

Dept 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, China

Objectives: Primary Sjögren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH.

Methods: We established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation. The case-control study was conducted with pSS-non-PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits.

Results: In total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non-PAH patients as controls. The presence of anti-SSB (p<0.001, OR 4.095) and anti-U1RNP antibodies (p<0.001, OR 29.518), the age of pSS onset (p<0.001, OR 0.651) and the positivity of corneal staining (p=0.003, OR 0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, hazard ratio (HR) 0.161), pulmonary vascular resistance (p=0.016, HR 1.105) and Sjögren's syndrome disease damage index (p=0.006, HR 1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p<0.0001).

Conclusion: The routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patient prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.
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http://dx.doi.org/10.1183/13993003.02157-2019DOI Listing
November 2020

Low expressions of PD-L1 and CTLA-4 by induced CD4CD25 Foxp3 Tregs in patients with SLE and their correlation with the disease activity.

Cytokine 2020 09 11;133:155119. Epub 2020 Jun 11.

The Laboratory Center for Basic Medical Sciences of Nanjing Medical University, Nanjing 211166, China. Electronic address:

Background: The induction of CD4CD25Foxp3 Treg from CD4CD25 T cells is deficient in the patients with systemic lupus erythematosus (SLE). Whether the induced CD4CD25Foxp3 Tregs possess defective function remains unclear. The purpose of the present research was to study the expression differences of functional membrane molecule between SLE patients and healthy controls by the induced CD4CD25Foxp3 Treg, in order to achieve a better understanding for the function deficiency of Treg in SLE.

Methods: Peripheral blood mononuclear cells (PBMCs) isolated from healthy donors and SLE patients were used to separated CD4CD25 T cells. These CD4CD25 T cells were induced to differentiate into CD4CD25Foxp3 Tregs through incubating with CD3 and CD28 antibodies, TGF-β, IL-2 and rapamycin in vitro. Flow cytometry was applied to analyze the expressions of PD-1, PD-L1, CTLA-4, mTGF-β, LAP, CD39, mIL-10 and cIL-10, by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs.

Results: (1) The induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs of both healthy controls and SLE patients both highly expressed PD-1. Nevertheless, the expressions of PD-L1 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were significantly lower than those in healthy controls, which were negatively correlated with SLEDAI; (2) The expressions of CTLA-4 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were also significantly reduced as compared with those in healthy controls, which were negatively correlated with SLEDAI; (3) As compared with healthy controls, the expressions of mTGF-β by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs were also reduced in SLE patients, but there was no significant difference between active and inactive patients. While the expressions of LAP between SLE patients and healthy controls did not show significant difference; (4) The expressions of CD39 and mIL-10 displayed scarce significant differences between healthy controls and SLE patients, while the expressions of cIL-10 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were significantly increased, which were not correlated with SLEDAI.

Conclusion: There were deficiencies in the expressions of PD-L1 and CTLA-4 in the induced CD4CD25Foxp3 Treg of SLE patients, which might be associated with the defective development and function of Treg involved in the pathological process of SLE.
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http://dx.doi.org/10.1016/j.cyto.2020.155119DOI Listing
September 2020

Serum uric acid is independently associated with aortic arch calcification in a cross-sectional study of middle-aged and elderly women.

Nutr Metab Cardiovasc Dis 2020 06 3;30(6):932-938. Epub 2020 Mar 3.

Division of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, China. Electronic address:

Background And Aims: The increased serum uric acid (SUA) level is associated with the prevalence of cardiovascular disease (CVD) risks. Aortic arch calcification (AAC) reflects subclinical coronary atherosclerosis and is linked to subsequent cardiovascular morbidity and mortality risks closely. To better understand the role of SUA on arteriosclerosis and CVD, we aim to determine the association between SUA and the presence of AAC.

Methods And Results: A total of 5920 individuals aged >45 years old without prior CVD disease were included. The prevalence rate of AAC was 14.4% in all participants and a significantly increasing trend for AAC prevalence rate was found across the SUA tertiles (p < 0.001 for trend). Subsequent subgroup analyses revealed that this positive association trend was only significant in female subjects. After adjusting for confounders, SUA is an independent predictor for the presence of AAC in overall participants and in women.

Conclusion: SUA is independently associated with AAC in middle-aged and elderly population, especially in the women. More research needs to determine whether lower thresholds for CVD risk screening for those middle-aged and elderly women with higher SUA tertile even without hyperuricemia are warranted.
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http://dx.doi.org/10.1016/j.numecd.2020.02.015DOI Listing
June 2020

Rheumotologitsts' view on the use of hydroxychloroquine to treat COVID-19.

Emerg Microbes Infect 2020 Dec;9(1):830-832

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.
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http://dx.doi.org/10.1080/22221751.2020.1760145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241459PMC
December 2020

Prognostic factors of pulmonary hypertension associated with connective tissue disease: pulmonary artery size measured by chest CT.

Rheumatology (Oxford) 2020 11;59(11):3221-3228

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing.

Objective: Pulmonary artery enlargement is a common manifestation of chest CT in patients with pulmonary arterial hypertension (PAH). The exact clinical significance of this phenomenon has not been clarified in connective tissue disease (CTD)-associated PAH (CTD-PAH). We aimed to explore the association between the dilatation of pulmonary artery and prognosis of CTD-PAH patients.

Methods: We retrospectively investigated 140 CTD-PAH patients diagnosed by echocardiography from 2009 to 2018. A chest multi-slice CT was performed on all the patients. Main pulmonary artery (MPA), right pulmonary artery (RPA), left pulmonary artery (LPA), ascending aorta (AAo) and descending aorta (DAo) diameters were measured. The ratios MPA/AAo and MPA/DAo were also calculated. The primary end point was all-cause mortality.

Results: During the observational period of 3.44 (0.23) years, 36 patients were followed to death. Cox univariate proportional hazard analysis showed that age, gender, MPA diameter, LPA diameter and RPA diameter were related to the risk of 5-year all-cause mortality in patients with CTD-PAH. In Cox multivariate proportional hazard analysis, MPA diameter and gender were predictors of all-cause mortality in CTD-PAH patients. An all-cause mortality risk prediction model revealed that baseline MPA diameter has the ability to predict 5-year all-cause mortality in CTD-PAH patients. Kaplan-Meier analysis showed that the 5-year survival rate was significantly lower in patients with MPA ≥37.70 mm (P ≤ 0.00012) compared with MPA ≤ 37.70 mm.

Conclusion: MPA diameter ≥37.70 mm measured by chest multi-slice CT was a potential independent risk factor of the poor long-term prognosis in Chinese CTD-PAH patients.
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http://dx.doi.org/10.1093/rheumatology/keaa100DOI Listing
November 2020

Association between comorbidities and extraglandular manifestations in primary Sjögren's syndrome: a multicenter cross-sectional study.

Clin Rheumatol 2020 Sep 7;39(9):2677-2688. Epub 2020 Mar 7.

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

Introduction: Primary Sjögren's syndrome (pSS) has been related to a higher risk of comorbidities, but studies examining comorbidities among patients with and without extraglandular manifestations are limited. The objectives of this study were to assess the prevalence of comorbidities in Chinese pSS patients and to determine the relationship between comorbidities and extraglandular manifestations.

Method: This cross-sectional study was based on the multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients fulfilling the 2002 American-European criteria or the 2016 classification criteria for pSS were enrolled from May 2016 to December 2018. Demographic data, disease characteristics, comorbidities (cardiovascular disease, thyroid disorder, malignancy, and fragility fracture), and extraglandular manifestations were collected. Multivariate analyses were used to assess the relationships between comorbidities and extraglandular manifestations.

Results: A total of 4087 pSS patients were included (95.7% female and mean age of 51.2 ± 13.1 years). The baseline prevalence of comorbidities was 3.8% for cardiovascular diseases, 12.1% for thyroid disorders, 1.8% for malignancies, and 1.7% for fragility fractures. The presence of extraglandular manifestations was associated with more comorbidities. Patients with more than one extraglandular manifestation had a higher prevalence of cardiovascular disease (adjusted odds ratio [aOR] 2.004, 95% confidence interval [CI] 1.221-3.288), thyroid disorder (aOR 1.380, 95% CI 1.022-1.863), and fragility fracture (aOR 2.684, 95% CI 1.505-4.786) after adjustment for age, sex, disease duration, and the significant variables in the univariate analysis.

Conclusions: The presence of extraglandular manifestations in pSS was associated with an increased comorbidity burden, especially cardiovascular disease, thyroid disorder, and fragility fracture. Key Points • This is the first study assessing the association between extraglandular manifestations and comorbidity burden based on the largest pSS registry in China. • Patients with multiple extraglandular manifestations tend to have increased comorbid cardiovascular disease, thyroid disorder, and fragility fracture.
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http://dx.doi.org/10.1007/s10067-020-04992-xDOI Listing
September 2020

A case of episodic and refractory arthritis due to a novel variant of NLRP12.

Ann Rheum Dis 2020 Feb 17. Epub 2020 Feb 17.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, China, Nanjing, Jiangsu, China

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http://dx.doi.org/10.1136/annrheumdis-2020-217023DOI Listing
February 2020

Evaluation of 12 different assays for detecting ANCA in Chinese patients with GPA and MPA: a multicenter study in China.

Clin Rheumatol 2019 Dec 14;38(12):3477-3483. Epub 2019 Aug 14.

Department of Clinical Immunology, Branch of Immune Cell Biology, State Key Discipline of Cell Biology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an, 710032, Shaanxi Province, China.

Objective: Due to lack of comprehensive evaluation for various detection methods for antineutrophil cytoplasmic antibody (ANCA) in Chinese population, we evaluate the diagnostic performance of 12 established analysis methods in Chinese patients having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Methods: Sera were collected from 209 patients with GPA or MPA and 243 diseases controls from 15 centers. Twelve different reagents were employed for C-ANCA, P-ANCA, myeloperoxidase (MPO)-ANCA, and proteinase 3(PR3)-ANCA detection. The accuracy, sensitivity, and specificity of each method were analyzed.

Results: The accuracy of the two indirect immunofluorescence (IIF) and two line immunoassay (LIA) was 0.838 and 0.874, 0.869, and 0.862, respectively. The accuracy of the eight quantitative antigen-specific immunoassays was varied from 0.867 to 0.967. The sensitivity of ANCA-associated vasculitis (AAV) was 0.770 and 0.761 for the two IIF, 0.727 and 0.718 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the sensitivity varied from 0.79 to 0.967. The specificity was 0.897 and 0.971 for the two IIF, 0.992 and 0.988 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the specificity of AAV varied from 0.963 to 0.983.

Conclusion: For Chinese patients suspected of having GPA and MPA, both the first-generation enzyme-linked immunosorbent assay (ELISA) and high-quality antigen-specific immunoassay can be used to detect MPO-ANCA and PR3-ANCA alone, without the combined detection with IIF to have good diagnostic performance. The chemiluminescent immunoassay (CLIA) seems to be a method worth recommending.Key points• Quantitative antigen-specific immunoassays can be used to detect MPO-ANCA and PR3-ANCA without IIF in Chinese.• CLIA has the maximum AUC value and the minimum LR (-) value, which seems to be a method worth recommending.
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http://dx.doi.org/10.1007/s10067-019-04736-6DOI Listing
December 2019

Simplified risk stratification for pulmonary arterial hypertension associated with connective tissue disease.

Clin Rheumatol 2019 Dec 5;38(12):3619-3626. Epub 2019 Aug 5.

Department of Rheumatology, The first affiliated hospital of Nanjing Medical University, Nanjing, China.

Objective: To explore the long-term prognostic value of a simplified risk assessment strategy based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines in Chinese patients with connective tissue disease (CTD) associated with pulmonary arterial hypertension (PAH).

Methods: We identified 50 CTD-PAH patients diagnosed by right heart catheterization. A retrospective chart review was completed to assess their clinical presentation and laboratory test results. A simplified version of the risk stratification model proposed by the 2015 ESC/ERS PH guidelines was applied, which included the WHO functional class, the 6-minute walking distance test, N-terminal pro-B-type natriuretic peptide plasma levels, pericardial effusion, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO). The risk grades were defined as follows: low risk = at least 3 low-risk variables and no high-risk variables; high risk = at least 2 high-risk variables, including SvO or CI; and intermediate risk = when the above definitions of low or high risk were not fulfilled. The study endpoint was 3-year all-cause mortality.

Results: Twenty patients were defined as a low-risk group, while 30 were classified into a combined intermediate-high-risk group at the baseline assessment. All 20 patients in the low-risk group remained in the low-risk group at follow-up, 20 patients in the intermediate-high-risk group were downgraded to the low-risk group, and eight patients remained in the intermediate-high-risk group at the follow-up assessment. Patients in the intermediate-high-risk group exhibited higher 3-year mortality than the low-risk group at baseline (26% vs 14%, P = 0.0384). Compared with patients who remained in the intermediate-high-risk group, patients who were downgraded to the low-risk group showed lower 3-year mortality (P = 0.0281).

Conclusion: A simplified risk stratification model based on the 2015 ESC/ERS PH guidelines helped to identify CTD-PAH patients with poor long-term  prognosis , which was useful in evaluating the severity and treatment response of patients with CTD-PAH.Key Point•This study showed that the simplified version of the 2015 ESC/ERS risk stratification model could help identify Chinese CTD-PAH patients with poor prognosis at diagnosis and after treatment initiation.
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http://dx.doi.org/10.1007/s10067-019-04690-3DOI Listing
December 2019

The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

Front Immunol 2019 24;10:884. Epub 2019 Apr 24.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analyses. The expression of osteoclasts (OCs), OCs-related cytokines, and immune cells in bone marrow were determined by flow cytometry, immunohistochemistry, immunofluorescence staining, and real-time PCR. The OCs formation was estimated using assays. MRI detected BME could emerge at day 25 in 70% mice after the first immunization ( = 10), when there were not any arthritic symptoms, histological or MRI synovitis. At day 28, BME occurred in 90% mice whereas the arthritic symptom and histological synovitis were only presented in 30 and 20% CIA mice at that time ( = 10). The emergence of BME was associated with an increased bone marrow OCs number and an altered distribution of OCs adherent to subchondral bone surface, which resulted in increased subchondral erosion and decreased trabecular bone number during the CIA process. Obvious marrow environment changes were identified after BME emergence, consisting of multiple OCs related signals, including highly expressed RANKL, increased proinflammatory cytokines and chemokines, and highly activated T cells and monocytes. BME reflects a unique marrow "osteoclastic environment," preceding the arthritic symptoms and synovitis during the development of CIA.
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http://dx.doi.org/10.3389/fimmu.2019.00884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491763PMC
October 2020

Adiponectin promotes fibroblast-like synoviocytes producing IL-6 to enhance T follicular helper cells response in rheumatoid arthritis.

Clin Exp Rheumatol 2020 Jan-Feb;38(1):11-18. Epub 2019 Apr 11.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objectives: Rheumatoid arthritis (RA) is characterised by the overproduction of autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. T follicular helper (Tfh) cells are a specialised Th subset that provides signals to B cells, promoting the secretion of antibodies. Our previous studies showed that the frequency of circulating Tfh cells were markedly increased in RA patients and positively correlated with disease activity and the levels of anti-CCP autoantibody. Adiponectin (AD) is an adipokine secreted mainly by adipocytes. Our previous work has demonstrated that AD is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in RA patients. However, it remains unknown whether AD aggravates the severity of RA via modulating Tfh cells. This study aims to investigate whether AD exerts effect on Tfh cells in RA.

Methods: CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), and adiponectin receptor 1 (AdipoR1) expression on the surface of CD4+CXCR5+PD-1+ (Tfh) cells was detected by flow cytometry. Purified HC CD4+ T cells were cultured with different concentration fetal bovine serun (FBS) in the presence or absence of AD. The percentages of Tfh cells were analysed by flow cytometry. RA or osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) were stimulated with AD for 72h and then co-cultured with HC CD4+ T cells through cell-to-cell contact or in a transwell system. The percentages of Tfh cells were analysed by flow cytometry and the levels of soluble factors such as interleukin-(IL)-6, IL-21, IL-12 and IFNγ in the supernatants were determined by Human Magnetic Bead Panel or Enzyme linked immunosorbent assay (ELISA). Then anti-IL-6 antibody and/or anti-IL-21 antibody was added to the co-culture system, and the percentages of Tfh cells were analysed by flow cytometry. The frequency of Tfh cells in the joint tissue of collagen-induced arthritis (CIA) mice was examined by flow cytometry. The mRNA expression of Tfh cell transcription factors and functional molecules such as B-cell lymphoma 6 (Bcl-6), B lymphocyte maturation protein 1 (Blimp-1), IL-6, IL-21, IL-12 and IFNγ in the joints of CIA mice were detected by real time PCR (RT-PCR).

Results: Adiponectin receptor 1 (AdipoR1) expression was detected on the surface of Tfh cells. However, in the present study, we did not find that AD has a direct effect on Tfh cell generation in vitro. Nonetheless, AD-stimulated RA FLSs could promote Tfh cell generation, predominantly via IL-6 production. And this upregulated effect was partially abolished upon neutralising IL-6. Finally, intraarticular injection of AD aggravated synovial inflammation with increased frequency of Tfh cells in the joints of AD-treated CIA mice.

Conclusions: Our study demonstrated that AD-stimulated RA FLSs promote Tfh cell generation, which is mainly mediated by the secretion of soluble factor IL-6. This finding reveals a novel mechanism for AD in RA pathogenesis.
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March 2020

Pulmonary arterial hypertension in systemic lupus erythematosus based on a CSTAR-PAH study: Baseline characteristics and risk factors.

Int J Rheum Dis 2019 May 11;22(5):921-928. Epub 2019 Feb 11.

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

Aim: Pulmonary arterial hypertension (PAH) is a complex and devastating complication of systemic lupus erythematosus (SLE). We sought to describe the baseline characteristics of right heart catheterization (RHC)-confirmed SLE-associated PAH and identify risk factors for PAH in SLE patients.

Methods: A multicenter, cross-sectional study was conducted using the Chinese SLE Treatment and Research group (CSTAR) registry. Baseline data for patients with SLE-associated PAH and SLE patients without PAH were collected and compared. Risk factors for PAH among patients with SLE were identified.

Results: A total of 292 patients with SLE-associated PAH were enrolled. RHC was used to reveal hemodynamic features, including mean pulmonary arterial pressure (46.2 ± 12.0 mm Hg), pulmonary arterial wedge pressure (7.84 ± 3.92 mm Hg), pulmonary vascular resistance (10.86 ± 5.57 Wood units), and cardiac index (2.77 ± 0.91 L/min × m ). A multivariate logistic regression analysis showed that serositis (odds ratio [OR] = 5.524, 95% CI 3.605-8.465, P < 0.001), anti-ribonucleoprotein (RNP) antibody positivity (OR = 13.332, 95% CI 9.500-18.710, P < 0.001), and diffusion capacity of carbon monoxide in the lung (DLCO)/%Pred <70% (OR = 10.018, 95% CI 6.619-15.162, P < 0.001) were independent predictors of PAH. We recommend using transthoracic echocardiography (TTE) to perform early screening of SLE patients who have serositis, anti-RNP antibody positivity, or DLCO/%Pred <70%. RHC is suggested for patients suspected of having PAH. Once a diagnosis of SLE-PAH is confirmed, evaluation and treatment should immediately begin.

Conclusion: Overall, we recommend performing early screening using TTE in SLE patients with serositis, anti-RNP antibodies, or a DLCO/%Pred <70%, even for patients in a relatively stable condition according to SLE disease activity index.
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http://dx.doi.org/10.1111/1756-185X.13478DOI Listing
May 2019

Long-term prognosis of patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Eur Respir J 2019 02 14;53(2). Epub 2019 Feb 14.

Dept 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.

This study aimed to identify the long-term clinical outcomes and prognostic factors of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) confirmed by right heart catheterisation.A multicentre prospective cohort of SLE-associated PAH was established. Baseline and follow-up records were collected. The primary end-point was death. The secondary exploratory end-point was treatment goal achievement (TGA), defined as an integrated outcome.In total, 310 patients were enrolled from 14 PAH centres. The 1-, 3- and 5-year survival rates were 92.1%, 84.8% and 72.9%, respectively. The 1-, 3- and 5-year TGA rates were 31.5%, 53.6% and 62.7%, respectively. Baseline serositis, 6-min walking distance >380 m and cardiac index ≥2.5 L·min·m were identified as independent prognostic factors of TGA. Patients with baseline serositis were more likely to reach TGA after intensive immunosuppressive therapy. TGA was identified as a positive predictor of survival in patients with SLE-associated PAH.TGA was associated with long-term survival, which supports the treat-to-target strategy in SLE-associated PAH. Baseline heart function predicted both survival and treatment goal achievement in patients with SLE-associated PAH. Patients with serositis at baseline tended to benefit from intensive immunosuppressive therapy and have a better clinical outcome.
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http://dx.doi.org/10.1183/13993003.00081-2018DOI Listing
February 2019

Association between Helicobacter pylori infection and Sjögren syndrome: A meta-analysis.

Medicine (Baltimore) 2018 Dec;97(49):e13528

First Clinical Medical College of Nanjing Medical University.

Background: Helicobacter pylori has been proved as a risk factor of many diseases. There are some researches trying to find connection between H. pylori and Sjögren syndrome (SS). However, the conclusions of these studies are controversial. We conducted this meta-analysis to evaluate the association between H. pylori and SS.

Methods: We searched PubMed and Embase databases for researches which include the data of H. pylori infection rate in SS and control groups. A fixed-effects model was used to analyze the risk odds ratio (OR) with 95% confidence intervals (CIs) according to the heterogeneity across the selected studies.

Results: Nine studies with 1958 participants including 619 patients with SS met the inclusion criteria. The total infection rate of H. pylori was 53.83% (1054/1958). We found that the patients with SS had a significantly higher H. pylori infection rate than control groups (OR = 1.19, 95% CI: 1.01-1.41, P = .033). Subgroup analysis demonstrated a significantly higher H. pylori infection rate in patients with primary SS than controls (OR = 1.24, 95% CI: 1.03-1.50, P = .026).

Conclusion: This meta-analysis is the 1st meta-analysis about the association between H. pylori and SS. The pooled data suggested a significantly higher H. pylori infection rate in patients with SS. More prospective or multicenter retrospective researches could be conducted in the future.
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http://dx.doi.org/10.1097/MD.0000000000013528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310521PMC
December 2018

Correction to: the efficacy and safety of total glucosides of peony in the treatment of primary Sjögren's syndrome: a multi-center, randomized, double-blinded, placebo-controlled clinical trial.

Clin Rheumatol 2019 02;38(2):617-618

Department of Rheumatology, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing, 100029, China.

The authors regret that the Fig. 1 in the original version of this article contained an error. In the left column, 211 cases in the TGP group should be followed up for 8 weeks before 12 weeks. The correct figure presented in this article.
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http://dx.doi.org/10.1007/s10067-018-4378-6DOI Listing
February 2019

Intraarticular injection of dexamethasone promotes bone erosion in collagen-induced arthritis in mice through up-regulation of RANKL expression.

Inflammopharmacology 2019 Jun 20;27(3):503-509. Epub 2018 Oct 20.

Department of Rheumatology, Jiangsu Province Hospital, Nanjing Medical University First Affiliated Hospital, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China.

Background: Dexamethasone (DEX) is an effective therapeutic option commonly used in the treatment of many inflammatory diseases. However, DEX could impair proliferation or differentiation of osteoblasts, suggesting a pivotal role of DEX in bone destruction.

Objective: To investigate whether intraarticular injection of DEX could exacerbate bone erosion during CIA development.

Setting: Collagen-induced arthritis (CIA) mice were divided into PBS-treated and DEX-treated groups (n = 5/group). Negative control group: DBA/1 mice (n = 5) were used as age-matched, healthy, untreated controls.

Method: CIA was induced in male DBA/1 mice. Intraarticular injected DEX (0.01 mg/Kg, 10 μl) into the knee joint of CIA on Day 28, Day 35, Day 42 and Day 49 post the 1st immunization.

Results: The severity of the arthritic disease was ameliorated in DEX-treated mice, accompanied by the decreased expression of IL-6, IL-8 and TNF-α. However, DEX treatment accelerates bone erosion and osteoporosis during CIA development and triggers higher expression of RANKL, IL-17 in vitro and vivo.

Main Outcome Measure: The effect of DEX on bone structure was analyzed using Haematoxylin & Eosin (H&E) staining and Micro-CT. The levels of receptor activator for nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) were investigated by real-time PCR, Western Blot and immunohistochemical analysis. RASFs were stimulated with Interleukin (IL)-1β and then treated with different concentrations of DEX for 72 h.

Conclusion: Intraarticular injection of DEX could exacerbate bone erosion in CIA model via up-regulation of RANKL expression.
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http://dx.doi.org/10.1007/s10787-018-0541-6DOI Listing
June 2019
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