Publications by authors named "Xiaofeng Zeng"

271 Publications

Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study.

Arthritis Res Ther 2021 04 7;23(1):102. Epub 2021 Apr 7.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease.

Objectives: This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia.

Methods: 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared.

Results: Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401).

Conclusions: Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.
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http://dx.doi.org/10.1186/s13075-021-02481-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025345PMC
April 2021

Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel.

Front Pharmacol 2021 17;12:619436. Epub 2021 Mar 17.

NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, China.

Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB , producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5'-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews-namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.
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http://dx.doi.org/10.3389/fphar.2021.619436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010131PMC
March 2021

Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China.

Orphanet J Rare Dis 2021 Mar 31;16(1):152. Epub 2021 Mar 31.

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

Background: Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement.

Results: CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups.

Conclusions: CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.
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http://dx.doi.org/10.1186/s13023-021-01780-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010942PMC
March 2021

Activation of Toll-Like Receptor 7 Signaling Pathway in Primary Sjögren's Syndrome-Associated Thrombocytopenia.

Front Immunol 2021 9;12:637659. Epub 2021 Mar 9.

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

To identify the importance of the Toll-like receptor (TLR) pathway using B cell high-throughput sequencing and to explore the participation of the TLR7 signaling pathway in primary Sjogren's syndrome (pSS)-associated thrombocytopenia in patient and mouse models. High-throughput gene sequencing and bioinformatic analyses were performed for 9 patients: 3 patients with pSS and normal platelet counts, 3 patients with pSS-associated thrombocytopenia, and 3 healthy controls. Twenty-four patients with pSS were recruited for validation. Twenty-four non-obese diabetic (NOD) mice were divided into the TLR7 pathway inhibition (CA-4948), activation (Resiquimod), and control groups. Serum, peripheral blood, bone marrow, and submandibular glands were collected for thrombocytopenia and TLR7 pathway analysis. Seven hub genes enriched in the TLR pathway were identified. Compared to that in control patients, the expression of interleukin (IL)-8 and TLR7 pathway molecules in B-cells was higher in patients with pSS-associated thrombocytopenia. Platelet counts exhibited a negative correlation with serum IL-1β and IL-8 levels. In NOD mice, CA-4948/Resiquimod treatment induced the downregulation/upregulation of the TLR7 pathway, leading to consistent elevation/reduction of platelet counts. Megakaryocyte counts in the bone marrow showed an increasing trend in the Resiquimod group, with more naked nuclei. The levels of IL-1β and IL-8 in the serum and submandibular gland tissue increased in the Resiquimod group compared with that in CA-4948 and control groups. pSS-associated thrombocytopenia may be a subset of the systemic inflammatory state as the TLR7 signaling pathway was upregulated in B cells of patients with pSS-associated thrombocytopenia, and activation of the TLR7 pathway led to a thrombocytopenia phenotype in NOD mice.
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http://dx.doi.org/10.3389/fimmu.2021.637659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986855PMC
March 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
March 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
February 2021

Inhibition of 5-lipoxygenase is associated with downregulation of the leukotriene B4 receptor 1/ Interleukin-12p35 pathway and ameliorates sepsis-induced myocardial injury.

Free Radic Biol Med 2021 Apr 9;166:348-357. Epub 2021 Mar 9.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China. Electronic address:

Sepsis rapidly contributed to multiorgan failure affecting most commonly of the cardiovascular and respiratory systems and yet there were no effective therapies. The current study aimed at providing evidence on the cardioprotection of suppression of 5-Lipoxygenase (5-Lox) and identifying the possible mechanism in the mouse model of sepsis. The cecal ligation-perforation (CLP) model was applied to C57BL/6 wild-type (WT) and 5-Lox deficient (5-Lox) mice to induce sepsis. 5-Lox expression was up-regulated in mouse myocardium and leukotriene B4 (LTB4) level was increased in serum after sepsis. Subsequently, we utilized a recombinant adenoviral expression vector (rAAV9) to overexpress Alox5 gene in adult mice. Compared to WT mice, 5-Lox overexpression accelerated CLP-induced myocardial injury and cardiac dysfunction. Oppositely, 5-Lox deficiency offered protection against myocardial injury in a mouse model of sepsis and attenuated sepsis-mediated inflammation, oxidative stress and apoptosis in the mouse heart. Mechanically, 5-Lox promoted LTB4 production, which in turn contributed to the activation of leukotriene B4 receptor 1 (BLT1)/interleukin-12p35 (IL-12p35) pathway and enhanced M1 macrophage polarization. However, the suppression of BLT1 by either gene mutation or antagonist U75302 significantly inhibited the adverse effect of 5-Lox in sepsis. Further study demonstrated that pharmacological inhibition of 5-Lox prevented CLP-induced septic cardiomyopathy (SCM). Our study identified 5-Lox exacerbated sepsis-associated myocardial injury through activation of LTB4 production and promoting BLT1/IL-12p35 pathway. Hence, inhibition of 5-Lox may be a potential candidate strategy for septic cardiac dysfunction treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.034DOI Listing
April 2021

Modeling and Simulation to Support Phase Ib/IIa Dose Selection for WBP216, A Long Half-Life Fully Human Monoclonal Antibody Against Interleukin-6.

Front Pharmacol 2021 18;12:617265. Epub 2021 Feb 18.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

WBP216 is an innovative IL-6 antibody, presenting high affinity to IL-6 and a long half-life (40-60 days). To optimize the dosage regimen for future clinical trials, pharmacokinetics (PK) and pharmacodynamics (PD) of WBP216 would be firstly characterized in Chinese rheumatoid arthritis (RA) patients. PK, CRP and DAS28 data of WBP216 were collected from 26 RA patients in a single ascending dose study. Non-linear mixed effects modeling was used for a population PK/PD analysis. A two-compartment model with a sequential zero-first order absorption and a first order elimination best described PK behavior of WBP216. Apparent systemic clearance was 0.015 L/h, central volume was 8.04 L. CRP as the fast-decreasing endpoint and DAS28 as the slow-reacting endpoint were both fitted well through an indirect response model. The baseline of ALT and free IL-6 were found associated with PK/PD parameters during covariates exploration. Simulation results confirmed that a loading dose regimen either of administration at weeks 0, 2, and 6 or doubling the maintenance dose level, followed by maintenance dosing of 75-150 mg every 8 weeks, was expected to provide a best risk/benefit ratio in future clinical studies. We hope this first PK/PD study of WBP216 in Chinese RA patients will help in the clinical development of WBP216 in future and provide a reference to the dosage optimization of similar antibodies with long half-life. CTR20170306.
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http://dx.doi.org/10.3389/fphar.2021.617265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930490PMC
February 2021

The modulatory roles of T cell glycosylation in systemic lupus erythematosus.

Clin Exp Rheumatol 2021 Feb 9. Epub 2021 Feb 9.

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, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science and Technology, Beijing, China.

Systemic lupus erythematosus (SLE) is a complex and challenging disorder. At present, abnormal T cells are considered to be the key point in the pathogenesis of SLE, including the losing central immune tolerance of self-reactive T cells in the thymus, breaking of regulatory T cell balances, and the overactivation of pro-inflammatory T cells. The alterations of T-cell receptor proteins are closely related to these abnormal changes. Glycosylation is one of the most ubiquitous steps of protein post-translational modification. Especially the modifications of N-glycans and O-glycans on T-cell surfaces have been found to regulate apoptosis and downstream signalling in SLE. Accordingly, this review summarises the aberrant modulate effects of T cell glycosylation in SLE and provides new insights into understanding the pathogenesis and some potential therapeutic targets of this chronic autoimmune disease.
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February 2021

Rheumatic immune-related adverse events associated with immune checkpoint inhibitors compared with placebo in oncologic patients: a systemic review and meta-analysis.

Ther Adv Chronic Dis 2021 12;12:2040622320976996. Epub 2021 Feb 12.

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

Objective: We aim to characterize the incidence and relative risk of rheumatic and systemic immune-related adverse effects (irAEs) among immune checkpoint inhibitor (ICI) therapy compared with those after placebo treatment.

Methods: Randomized clinical trial studies with placebo control with the following keywords were searched from Embase, PubMed, Cochrane databases: immune checkpoint inhibitors, neoplasms, randomized controlled trials, and adverse effects.

Results: Among the 5444 published and 316 registration records, nine placebo-controlled randomized clinical trials met our selection criteria, and included data from 5560 patients. Compared with placebo use, using ICIs increases the risk of overall-rheumatic irAEs. The incidence and relative risk of all-grade rheumatic irAEs were 18.40% [95% confidence interval (CI) 12.16-25.59%,  < 0.01] and 2.30 (95% CI 1.32-4.02), respectively, while musculoskeletal irAEs were 11.30% (95% CI 9.76-12.85%) and 1.01 (95% CI 0.84-1.22). The incidence and relative risk of severe rheumatic irAEs were 5.72% (95% CI 3.92-7.82%), and 8.29 (95% CI 3.75-18.35), respectively. Arthralgia was the most common rheumatic irAE (incidence 11.00%, 95% CI 9.55-12.64%; relative risk 0.99, 95% CI 0.82-1.19), although usually not severe. Colitis (incidence 3.23%, 95% CI 1.27-7.98%; relative risk 6.53, 95% CI 2.66-16.04) and pneumonitis (incidence 3.11%, 95% CI 1.56-6.21; relative risk 4.04, 95% CI 1.65-9.89) were commonly observed and tended to be severe. Hepatitis, hypophysitis, thyroiditis, and myositis were rare and less recorded, yet can be severe and life threatening. Other extremely rare severe rheumatic irAEs included sarcoidosis ( = 11), autoimmune arthritis ( = 8), autoimmune uveitis ( = 3), autoimmune pericarditis, bursitis, osteochondrosis, psoriasis, polymyalgia rheumatica, systemic inflammatory response syndrome, and Sjögren syndrome ( = 1, each).

Conclusion: ICI therapy increased the incidence and relative risk of all-grade and severe rheumatic irAEs. Arthralgia was the most commonly observed non-severe irAE, while colitis and pneumonitis were commonly observed severe irAEs. Rare rheumatic irAEs like hepatitis, hypophysitis, thyroiditis, and myositis warrant special attention.
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http://dx.doi.org/10.1177/2040622320976996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887685PMC
February 2021

Plasticity of Treg and imbalance of Treg/Th17 cells in patients with systemic sclerosis modified by FK506.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:2058738421998086

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

To determine the effects of Tacrolimus (FK506) on Treg cells and subpopulations in SSc patients and assess the ability of FK506 to modify the immune imbalance of Treg/Th17 cells. We analyzed PBMC from five SSc patients and six healthy control by flow cytometry after cultured with 0, 0.1, 1, or 10 ng/ml FK506 in vitro. The number of Treg cells decreased in SSc patients treated with FK506. The number of FrI cells were decreased in SSc following FK506 treatment. The drug did increase the frequency of FrII/Treg cells, but not FrII cells. However, FK506 significantly decreased FrIII in both SSc patients and controls. FK506 clearly decreased the numbers of Th17 cells and FoxP3IL-17 cells. The proliferation capacity of cells was also inhibited by FK506, which had a greater effect on FoxP3 cells than FoxP3 cells. FK506 did inhibit the proliferation of FrIII cells, but not FrI or FrII cells. Our study provides that FK506 reduced the number of FoxP3 CD45RA T cells (FrIII) by inhibiting its proliferation. Therefore, FK506 modifies Treg cells and the immune imbalance between Tregs and Th17 cells in SSc patients.
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http://dx.doi.org/10.1177/2058738421998086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917869PMC
February 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

The protective effect of gastrodin against the synergistic effect of HIV-Tat protein and METH on the blood-brain barrier via glucose transporter 1 and glucose transporter 3.

Toxicol Res (Camb) 2021 Jan 22;10(1):91-101. Epub 2021 Jan 22.

School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong, Kunming, Yunnan 650500, China.

Many individuals infected with human immunodeficiency virus (HIV) are also afflicted with HIV-associated neurocognitive disorders (HANDs). Methamphetamine (METH) abuse puts HIV-1 patients at risk for HANDs because METH and HIV-1 proteins, such as trans-activator of transcription (Tat), can synergistically damage the blood-brain barrier (BBB). However, the underlying mechanism of METH- and HIV-Tat-induced BBB damage remains unclear. In this study, male adult tree shrews and human brain capillary endothelial cells were treated with HIV-Tat, METH, and gastrodin. We used western blotting to examine the expressions of glucose transporters (GLUT1 and GLUT3), tight junctions, and junctional adhesion molecule A (JAMA) and to evaluate the damage and detect Evans blue (EB) and fluorescein sodium in the brain to assess BBB permeability to study the effect of METH and the HIV-1 Tat protein on BBB function and . The results showed that the group treated with Tat and METH experienced a significant change at the ultrastructural level of the tree shrew cerebral cortex, decreased protein levels of occluding, claudin-5, Zonula occludens 1 (ZO1), and JAMA and , and increased levels of EB and fluorescein sodium in the tree shrew cerebral cortex. The protein levels of GLUT1 and GLUT3 was downregulated in patients with Tat- and METH-induced BBB damage. Pretreatment with gastrodin significantly increased the levels of EB and fluorescein sodium in the tree shrew cerebral cortex and increased the expressions of occluding, ZO1, JAMA, and GLUT1 and GLUT. These results indicate that gastrodin may offer a potential therapeutic option for patients with HANDs.
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http://dx.doi.org/10.1093/toxres/tfaa102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885197PMC
January 2021

Cardiac manifestations of eosinophilic granulomatosis with polyangiitis from a single-center cohort in China: clinical features and associated factors.

Ther Adv Chronic Dis 2021 22;12:2040622320987051. Epub 2021 Jan 22.

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

Background: Cardiac manifestations are common and life-threatening in eosinophilic granulomatosis with polyangiitis (EGPA), which remains poorly studied in China. We aim to investigate its clinical features, associated factors, treatment, and outcomes.

Methods: We reviewed the clinical records of 110 EGPA patients and examined the independent factors associated with cardiac manifestations using multivariate logistic regression. Receiver operating characteristic curves determined the cut-off values, and survival was calculated Kaplan-Meier curves.

Results: Cardiac involvement was present in 36.4% (40/110) of EGPA patients, which mainly manifested as pericardial effusion (16.4%, 18/110), myocardial involvement (13.6%, 15/110), and heart failure (8.2%, 9/110). The mean age was 42.1 ± 14.23 years with no female/male predominance. Compared with the cardiac-unaffected group, the cardiac-affected group showed a lower rate of biopsy-proved vasculitis (0% 20%,  = 0.002). The eosinophil count [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.029-1.267] was independently associated with cardiac manifestations in EGPA, with a cut-off value of 3.66 × 10/L [area under the curve (AUC) = 0.692,  = 0.001]. Regarding treatment, the cardiac-affected group displayed a higher ratio of glucocorticoid pulse combined with intravenous cyclophosphamide (CYC-IV) (40% 21.4%,  = 0.037), and intravenous immunoglobulin combined with glucocorticoid plus CYC-IV (17.5% 4.3%,  = 0.035) than the control group. Outcomes ( = 0.131) and survival ( = 0.1972) were not significantly different between the groups.

Conclusion: In this single-center Chinese EGPA cohort, cardiac manifestations are observed in 36.4% of patients, which primarily presents as myocardial involvement, pericardial effusion, and heart failure, independently associated with eosinophil count. Glucocorticoid combined with cyclophosphamide is the treatment cornerstone for EGPA patients with cardiac manifestations.
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http://dx.doi.org/10.1177/2040622320987051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841702PMC
January 2021

Ultra-microangiography in evaluating the disease activity of rheumatoid arthritis and enhancing the efficacy of ultrasonography: A preliminary study.

Eur J Radiol 2021 Apr 26;137:109567. Epub 2021 Jan 26.

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address:

Objective: Ultra-microangiography (UMA) is a novel Doppler technique that has high sensitivity for low-velocity blood flows. In this study, a distinctive imaging feature, penetrating blood vessels on the surface of eroded bones within the inflamed joints, was observed on UMA. We aimed to investigate the feasibility of UMA in assessing disease activity and identify the clinical value of the UMA feature for evaluating rheumatoid arthritis (RA).

Methods And Materials: Power-Doppler ultrasound (PDUS) and UMA were performed on small joints of RA patients. The semiquantitative scores of PDUS and UMA of the joints were assessed and compared. The UMA imaging feature of penetrating vessels on the surface of eroded bones was evaluated, and the patients were divided into three groups based on imaging features. (Group 1: no inflammatory signs; Group 2: inflammatory US features but no UMA features; and Group 3: detected UMA features). The correlations between the groups and clinical parameters were assessed.

Results: A total of 52 patients with RA were recruited, with 364 joints (MCP, PIP, MTP and wrist) scanned. Synovial blood vessel signals were detected for 68 by PDUS and for 93 by UMA (display rate of blood vessel signals: 18.68 % VS 25.55 %). UMA presented better display capability of blood vessels within the inflamed regions than that of PDUS in overall. Significant differences were detected in clinical scores (P < 0.0001 for DAS28 [ESR], DAS28 [CRP], SDAI, CDAI, CRP P = 0.0303, SJC P = 0.0059, and TJC P = 0.0423) between Group 2 and 3. Significant correlations between the groups and clinical parameters were also observed (DAS28 [ESR] ρ=0.750; DAS28 [CRP] ρ=0.762; SDAI ρ=0.778; CDAI ρ=0.773; CRP ρ= 0.524; SJC ρ=0.742; TJC ρ=0.693, P < 0.0001), indicating that the UMA feature was related to high disease activity.

Conclusions: UMA can help enhance the detection rate of micro-vascularization. The UMA feature of the penetrating vessels on the surface of eroded bones is likely to be associated with severe disease activity.
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http://dx.doi.org/10.1016/j.ejrad.2021.109567DOI Listing
April 2021

Aberrant monocyte subsets in patients with Behçet's disease.

Clin Immunol 2021 Apr 5;225:108683. Epub 2021 Feb 5.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Shuaifuyuan, Dongcheng District, Beijing 100730, China. Electronic address:

Monocytes are a versatile and dynamic population, but its implication in Behçet's Disease (BD) remains elusive. We investigated the proportion, phenotypical and functional alterations in classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM) subsets in BD. A higher IM and lower NCM population in BD patients were noted, closely correlated with disease activity, and rescued after treatment. CD11b and CD64 expression on CM, IM and NCM in BD were enhanced. BD CM promoted TNF-a and IL-6 production and facilitated Th1 differentiation. BD IM promoted IL-6 production. We further demonstrated a higher level of phosphorylated p65 (p-p65) in BD CM and increased p-p65 and p-p38 in BD IM. Our data highlighted the aberrant populations of IM and CM in BD, potentially implicated in BD' pathogenesis.
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http://dx.doi.org/10.1016/j.clim.2021.108683DOI Listing
April 2021

Clinical Features and Outcomes of Neuropsychiatric Systemic Lupus Erythematosus in China.

J Immunol Res 2021 18;2021:1349042. Epub 2021 Jan 18.

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, No. 1 Shuaifuyuan, Beijing 100730, China.

Objective: To identify the clinical characteristics, magnetic resonance imaging (MRI) results, and prognostic factors of neuropsychiatric (NP) systemic lupus erythematosus (SLE; NPSLE) in a relatively large patient series in China.

Methods: Data of patients with NPSLE at Peking Union Medical College Hospital (PUMCH) were collected retrospectively from June 2012 to June 2016. NPSLE patients were compared with 220 non-NPSLE patients. Survival rates were evaluated using the Kaplan-Meier curves, log-rank test, and Cox proportional hazards modeling. Cranial MRI results were also studied.

Results: Of the 194 included patients, sixteen subtypes of NPSLE were identified, and the most common manifestations were seizure (36.6%), acute confusional state (25.3%), and cerebral vascular disease (15.5%). Compared with the non-NPSLE group, NPSLE patients were significantly more likely to have typical lupus symptoms, higher Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores ( = 0.002), and positive rate of anti-ribosomal P protein antibodies ( = 0.008). Patients with seizure were more likely to have higher SLEDAI-2K scores and positive anti-2GP1 than non-NPSLE patients. Sixteen patients died during follow-up. The most common cause of death was infection (37.5%). NPSLE significantly decreased survival rates of SLE patients. Patients with elevated serum creatinine ( = 0.001), hypocomplementemia ( = 0.031), and SLEDAI - 2K scores ≥ 15 ( = 0.014) had shorter survival periods. Eighty-two patients underwent detailed cranial MRI analysis; of these, 50 (61.0%) had abnormal results. Small vessel disease was the most common abnormal finding, followed by inflammatory-like lesions and large vessel disease.

Conclusions: High disease activity and positive rate of anti-ribosomal P protein antibodies may be risk factors for NPSLE. NPSLE decreases survival rates of SLE patients. Renal insufficiency and high disease activity are predictive of poor prognoses for NPSLE patients.
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http://dx.doi.org/10.1155/2021/1349042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834780PMC
January 2021

Tonsillitis as a possible predisposition to synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome.

Int J Rheum Dis 2021 Apr 27;24(4):519-525. Epub 2021 Jan 27.

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

Aim: To present the prevalence of tonsillitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) patients, to compare the clinical characteristics and disease activities between SAPHO patients with and without tonsillitis and to preliminarily explore the efficacy of tonsillectomy in SAPHO syndrome.

Method: A total of 58 SAPHO patients were included. Clinical data were collected, including demographic characteristics and acute phase reactants (erythrocyte sedimentation rate, high-sensitivity C-reactive protein). The visual analog scale (VAS), Palmoplantar Pustule Psoriasis Area Severity Index (PPPASI) and Nail Psoriasis Severity Index (NAPSI) were used to measure the severity of bone pain, skin lesions and nail lesions, respectively. Patients were referred to the otolaryngology department for tonsil examinations, including tonsil hypertrophy (grade ≥ 2), chronic congestion, inflammatory secretion and tonsil stones. The patients who underwent tonsillectomy were followed up after the surgery.

Results: A total of 67.2% of patients had tonsillitis. Patients with tonsillitis had markedly higher PPPASI (1.2 [0, 7.4] vs. 7.6 [1.75, 15.5], P = .018) and NAPSI (0 [0, 21] vs. 8 [3, 28], P = .032) scores. After tonsillectomy, the patients experienced significantly improved bone pain (VAS, 5 [4, 7] vs. 3 [1, 4], P = .034) and skin lesions (PPPASI, 16.2 [7.05, 18.35] vs 1.8 [0.7, 3.7], P = .028).

Conclusion: Approximately 2/3 of SAPHO patients had tonsillitis. Patients with tonsillitis had more severe skin and nail lesions. Tonsillectomy might be associated with improved bone and skin symptoms in SAPHO patients. Future prospective controlled studies are warranted.
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http://dx.doi.org/10.1111/1756-185X.14064DOI Listing
April 2021

Activation of Toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction.

Clin Transl Med 2021 Jan;11(1):e266

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.

Background: As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy.

Methods: We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7-knockout (TLR7 ), wild-type (WT) mice, cardiac-specific TLR7-transgenic (cTG-TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad-TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca imaging, western blotting, immunostaining, and quantitative real-time polymerase chain reaction (qPCR).

Results: We found that TLR7 knockout markedly exacerbated sepsis-induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7 mice displayed weaker Ca handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS-induced systolic dysfunction, and loxoribine (TLR7-specific agonist) improved LPS-induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)-protein kinase A (PKA) pathway, which upregulated phosphorylate-phospholamban (p-PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca handling in response to sepsis. While improved Ca handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG-TLR7 mice. Consistently, TLR7 overexpression improved LPS-induced Ca -handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype.

Conclusions: Our data demonstrated that activation of TLR7 protected against sepsis-induced cardiac dysfunction through promoting cAMP-PKA-PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.
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http://dx.doi.org/10.1002/ctm2.266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775988PMC
January 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

Comparison of Clinical Features in HLA-B27 Positive and Negative Patients With Axial Spondyloarthritis: Results From a Cohort of 4,131 Patients.

Front Med (Lausanne) 2020 23;7:609562. Epub 2020 Dec 23.

Department of Rheumatology, Xinxiang Central Hospital, Xinxiang, China.

The aim of our study was to assess the influence of the HLA-B27 status on axial spondyloarthritis (axSpA) in the largest cohort in China. An observational, cross-sectional, and analytic study of axSpA patients from the China axSpA database was performed. Demographic and clinical data were compared in terms of the HLA-B27 status. Univariate and multivariate analyses were performed to identify variables related to HLA-B27 presence. We enrolled 4,131 patients in this study; of those, 36,95 (89.4%) were HLA-B27 positive. In the multivariate analysis, male gender ( < 0.001), younger age ( < 0.001), a disease duration of more than 3 years ( < 0.001), a family history of SpA ( < 0.001), uveitis ( < 0.001), ASDAS-CRP ( < 0.001), and biologic treatment ( < 0.001) were the main variables that were independently related to HLA-B27 presence, whereas a diagnosis delay time >36 months ( < 0.001) and psoriasis ( < 0.001) were independently related to HLA-B27 absence. In Chinese axial SpA patients, presence of HLA-B27 is associated with the male sex, younger age, longer disease duration, greater family aggregation, and higher frequency of uveitis; absence of HLA-B27 is associated with longer diagnosis delay time and higher frequency of psoriasis.
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http://dx.doi.org/10.3389/fmed.2020.609562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785867PMC
December 2020

Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population.

Front Med (Lausanne) 2020 10;7:583944. Epub 2020 Dec 10.

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

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement. We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement. The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively, = 0.039), higher eosinophil count (median [IQR]: 5810 [4020-11090] vs. 2880 [1530-6570] n/μL, respectively, = 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16-28] vs. 15 [12-18], respectively, = 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively, = 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up. Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.
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http://dx.doi.org/10.3389/fmed.2020.583944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793957PMC
December 2020

Tocilizumab for Refractory Rapidly Progressive Interstitial Lung Disease Related to Anti-MDA 5-positive Myositis.

Rheumatology (Oxford) 2021 Jan 7. Epub 2021 Jan 7.

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.

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http://dx.doi.org/10.1093/rheumatology/keaa906DOI Listing
January 2021

Tripterygium wilfordii Hook F. in the treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a clinical trial.

Clin Rheumatol 2021 Jan 3. Epub 2021 Jan 3.

Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China.

Objective: This study aimed to investigate the efficacy and safety of Tripterygium wilfordii Hook F. (TwHF) in the treatment of osteoarticular lesions in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Methods: Eligible SAPHO patients were recruited to this single-center trial to receive 12-week TwHF treatment. Two dose groups (1.0-mg/kg/day group and 1.5-mg/kg/day group) were designed and patients were allocated (1:1) to these two groups. The primary endpoint was the change from baseline in Ankylosing Spondylitis Disease Activity Score on the basis of C-reactive protein level (ASDAS) at week 12.

Results: All the 30 included patients completed the trial. At week 12, both dose groups showed significant change from baseline in ASDAS (1.0-mg/kg/day group: - 1.34 (1.10), p = 0.000; 1.5-mg/kg/day group: - 1.53 (1.19), p = 0.000). Similar improvement was also found in the Visual Analogue Scale in global osteoarticular pain, Bath Ankylosing Spondylitis Disease Activity Index, and other efficacy measures. The results showed a fast-acting characteristic of TwHF that the maximum efficacy was achieved within the first 2-4 weeks and maintained at a stable level for the rest of the study. No significant differences were observed between the two dose groups under the current sample size. TwHF was well tolerated that no severe adverse events or irregular menstruation were recorded, except for one patient who developed severe alanine aminotransferase elevation at the last follow-up and has stopped the TwHF treatment after the 12-week follow-up.

Conclusions: TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value.

Trial Registration: ChiCTR1900025912 Key points • This is the first clinical trial to evaluate Tripterygium wilfordii Hook F. (TwHF) in the treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. • Twelve-week TwHF treatment in both dose groups designed (1.0-mg/kg/day group and 1.5-mg/kg/day group) was well tolerated and could lead to significant disease remission of SAPHO syndrome. • No significant differences were observed between the two dose groups under the current sample size. • TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value.
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http://dx.doi.org/10.1007/s10067-020-05562-xDOI Listing
January 2021

Changes in Efficacy Indicators for Adalimumab Biosimilar Candidate (HS016) for the Treatment of Active Ankylosing Spondylitis at Various Time Points.

Front Pharmacol 2020 7;11:606497. Epub 2020 Dec 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 and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 ( = 416) or adalimumab ( = 232) for active ankylosing spondylitis (AS) patients was comparable. In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab. The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period. This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all < 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment. The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial. http://www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520].
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http://dx.doi.org/10.3389/fphar.2020.606497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750525PMC
December 2020

UPLC-MS based plasma metabolomics and lipidomics reveal alterations associated with IgG4-related disease.

Rheumatology (Oxford) 2020 Dec 20. Epub 2020 Dec 20.

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

Objective: The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD.

Methods: Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were collected. Plasma was measured for ultraperformance liquid chromatography-tandem mass spectrometry based metabolomics and lipidomics profiling. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers. The receiver operating characteristic and the correlations between biomarkers and clinical parameters were investigated.

Results: The plasma metabolites are altered among healthy controls, newly diagnosed IgG4-RD and post-treated IgG4-RD groups. Of the identified features, eight metabolites were significantly perturbed in the IgG4-RD group, including glyceric acid 1,3-biphosphate (1,3-BPG), uridine triphosphate (UTP), uridine diphosphate glucose (UDP-Glc) or uridine diphosphate galactose (UDP-Gal), lysophospholipids, linoleic acid derivatives and ceramides. Receiver operating characteristic analysis indicated that UTP, UDP-Glc/UDP-Gal and LysoPC (18:1) had high sensitivity and specificity in diagnosis of IgG4-RD. A Pearson correlation analysis showed that 1,3-BPG and UTP were strongly correlated with clinical parameters.

Conclusion: IgG4-RD patients have a unique plasma metabolomic profile compared with healthy controls. Our study suggested that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers for diagnosis of IgG4-RD.
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http://dx.doi.org/10.1093/rheumatology/keaa775DOI Listing
December 2020