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Clinical correlations with disease-associated auto-antibodies in a Chinese cohort with systemic sclerosis

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Chinese Medical Journal 2022年第15期135卷 1878-1880页

作者： Sen Yang Minrui Liang Chen Chen Wenjing Ye Xiaoxia Zhu Yu Xue Ning Kong Yiyun Yu Dandan Xuan Shucong Zheng Xue Yang Zaihua Zhu Tianyi Zhao Weiguo Wan Hejan Zou Division of rheumatology Huashan HospitalFudan UniversityShanghai 200040China Institute of Rheumatology Immunology and AllergyFudan UniversityShanghai 200040China

To the Editor:Systemic sclerosis(SSc)is an autoimmune disease characterized by,progressive skin and visceral fibrosis,microvasculopathy,and autoimmunity.Circulating auto-antibodies(AAbs)are detectable in 90%to 95%of p... 详细信息

关键词： antibodies sclerosis autoimmune

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies:a systematic review and meta-analysis

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Chinese Medical Journal 2020年第8期133卷 982-993页

作者： Li Zhao Ling Cao Tian-Yi Zhao Xue Yang Xiao-Xia Zhu He-Jian Zou Wei-Guo Wan Yu Xue Department of rheumatology Huashan HospitalFudan UniversityShanghai 200040China Institute of Rheumatology Immunology and AllergyFudan UniversityShanghai 200040China

Background:Hyperuricemia and gout have become public health concerns;many important guidelines have recommended xanthine oxidase inhibitors(XOIs)as the first-line urate-lowering therapies(ULTs)to treat chronic gout with hyperuricemia.However,whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial.The aim of this study was to assess the incident risk of cardiovascular(CV)events(CVE)in hyperuricemia population,assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups,and specify the safety of different ULTs.Methods:We searched PubMed,Embase,the Cochrane Library,Wanfang,Chongqing VIP(CQVIP,***),and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials(RCTs)in English and Chinese.Potential medications included XOIs,and uricosurics.RCTs were divided into sub-groups analysis based on blinding status and patients’history of CV diseases.Risk ratios(RRs)were calculated and were reported with corresponding 95%confidence intervals(CIs)by fixed-effects or random-effects model.Results:Seven prospective cohort studies and 17 RCT studies were included.The risks of both major adverse cardiovascular events(MACE)(RR=1.72,95%CI 1.28-2.33)and CVE(RR=1.35,95%CI 1.12-1.62)were higher in the hyperuricemia population than non-hyperuricemia one.In seven RCT studies where XOIs were compared with no-treatment or placebo,the results of five low CV risk studies showed that XOIs lowered the risks of both MACE(RR=0.35,95%CI 0.20-0.62)and CVE(RR=0.61,95%CI 0.44-0.85);whereas two high CV risk studies showed that XOIs lowered the risk of CVE(RR=0.69,95%CI 0.54-0.88)rather than MACE(RR=0.62,95%CI 0.29-1.35).In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared,no statistical difference was found in the risk of MACE or CVE.Conclusions:The hyperuricemia population does have a higher incidence of CVE,and the results suggeste

关键词： Hyperuricemia Gout Cardiovascular event Febuxostat Allopurinol

Mechanism-driven strategies for prevention of rheumatoid arthritis

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rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： V.Michael Holers Kristine A.Kuhn M.Kristen Demoruelle Jill M.Norris Gary S.Firestein Eddie A.James William H.Robinson Jane H.Buckner Kevin D.Deane Division of rheumatology University of Colorado School of MedicineAuroraColoradoUSA Department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA Division of rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research institute SeattleWashingtonUSA Division of Immunology and rheumatology Stanford UniversityStanfordCaliforniaUSA Department of Medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR)

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Chinese Medical Journal 2023年第8期136卷 951-958页

作者： Fan Yang Chaofan Lu Huilan Liu Lei Dou Yanhong Wang Hongbin Li Xinwang Duan Lijun Wu Yongfu Wang Xiuying Zhang Jian Xu Jinmei Su Dong Xu Jiuliang Zhao Qingjun Wu Mengtao Li Xiaomei Leng Xiaofeng Zeng Department of rheumatology and Clinical Immunology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Key Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China Department of rheumatology and Immunology The Second People’s Hospital of WuhuWuhuAnhui 241000China Department of Epidemiology and Biostatistics Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China The Division of rheumatology The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner Mongolia 010110China Department of rheumatology The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Department of rheumatology and Immunology The People’s Hospital of the Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China Department of rheumatology First Affiliated Hospital of Baotou Medical CollegeBaotouInner Mongolia 014010China Department of rheumatology Zibo Central HospitalZiboShandong 255036China Department of rheumatology The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China

Background:The clinical features of enthesitis in patients with psoriatic arthritis(PsA)have been reported in some Western countries,but data in China are very limited.This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.Methods:Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis(CREPAR)(December 2018 to June 2021)were included.Data including demographics,clinical characteristics,disease activity measures,and treatment were collected at enrollment.Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada(SPARCC),Maastricht ankylosing spondylitis enthesitis score(MASES),and Leeds enthesitis index(LEI)indices.A multivariable logistic model was used to identify factors related to enthesitis.We also compared our results with those of other cohorts.Results:In total,1074 PsA patients were included,308(28.7%)of whom had enthesitis.The average number of enthesitis was 3.3±2.8(range:1.0–18.0).More than half of the patients(165,53.6%)had one or two tender entheseal sites.Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis,reported a higher proportion of PsA duration over 5 years,and had a higher percentage of axial involvement and greater disease activity.Multivariable logistic regression showed that axial involvement(odds ratio[OR]2.21,95%confidence interval[CI],1.59–3.08;P<0.001),psoriasis area and severity index(PASI)(OR:1.03,95%CI:1.01–1.04;P=0.002),and disease activity score 28-C reactive protein(DAS28-CRP)(OR:1.25,95%CI:1.01–1.55;P=0.037)were associated with enthesitis.Compared with the results of other studies,Chinese patients with enthesitis had a younger age,lower body mass index(BMI),a higher rate of positive human leukocyte antigen(HLA)-B27,more frequent dactylitis,and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs’(csDMARDs)use.Conclusions:Enthesitis is a common condition among Chinese patients with PsA.It is import

关键词： Enthesitis Psoriatic arthritis Registry

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

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BIOCELL 2024年第1期48卷 9-19页

作者： YANG LI JIAN LIU YUEDI HU CHENGZHI CONG YIMING CHEN QIAO ZHOU Department of rheumatology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230031China First Clinical Medical School Anhui University of Chinese MedicineHefei230031China Institute of Rheumatology Anhui Academy of Chinese MedicineHefei230031China

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

关键词： Rheumatoid arthritis Neutrophil extracellular traps Review

Polylysine complexes and their biomedical applications

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再生工程(英文)

再生工程(英文) 2023年第1期4卷 20-27页

作者： Haofang Zhu Rui Liu Yixuan Shang Lingyun Sun Department of rheumatology and Immunology Institute of Translational MedicineThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China

Poly-L-lysine(PLL)is a water-soluble biopolymer consist of repeating unit of L-lysine.It displays intrinsic non-antigenicity,antibacterial property,biocompatibility,and biodegradability,and facile synthesis procedure,there-fore has attracted particular attention in various biomedical and pharmaceutical applications.Following a brief introduction to PLL synthesis,this review focuses on the significant advances of PLL and PLL-derived complexes utilized in cargo delivery,tissue adhesives,and antibacterial materials.Meanwhile,this review summarized the modification and optimization of PLL complexes for further clinical translational studies.The final section dis-cusses the challenges and opportunities of PLL-based complexes in the biomedical areas.

关键词： Polylysine cargo delivery bioadhesive antibacterial biomedicine

Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression

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Cellular & Molecular Immunology 2022年第10期19卷 1130-1140页

作者： Tihong Shao Patrick S.C.Leung Weici Zhang Koichi Tsuneyama William M.Ridgway Howard A.Young Zongwen Shuai Aftab A.Ansari M.Eric Gershwi Department of rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Division of rheumatology Allergyand Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavisCAUSA Department of Pathology and Laboratory Medicine Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan Center for Cancer Research National Cancer Institute-FrederickFrederickMDUSA

The interferon(IFN)signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity.We have generated a unique murine model named ARE-Del,with chronic overexpression of IFNγ,by altering IFNγmetabolism.Importantly,these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis,including high titers of autoantibodies and portal inflammation.We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis.To study this hypothesis,ARE-Del^(+/−)mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied.JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage,associated with a significant reduction in splenic and hepatic CD4^(+)T cells and CD8^(+)T cells.Functionally,ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγand TNF from splenic CD4^(+)T cells.Additionally,ruxolitinib treatment also decreased the frequencies of germinal center B(GC B)cells and T follicular helper(Tfh)cells and led to lower serological AMA levels.Of note,liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment.Mechanistically,ruxolitinib inhibited the secretion of IL-6,TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro,indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway.Our data highlight the significance,both immunologically and clinically,of the JAK/STAT signaling pathway in autoimmune cholangitis.

关键词： Primary biliary cholangitis Autoimmunity Interferons Janus Kinase Inhibitors Ruxolitinib

Classifying rheumatoid arthritis by Traditional Chinese Medicine Zheng: a multi-center cross-sectional study

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Journal of Traditional Chinese Medicine 2019年第3期39卷 425-432页

作者： Wang Weijie Tang Xiaopo Wang Xinchang Jiang Quan Fan Yongsheng Department of rheumatology The Second Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou 310005 China Department of rheumatology Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China Institute of Rheumatology Zhejiang Chinese Medical University Hangzhou 310053 China

OBJECTIVE:To assess the relationship between disease symptoms and traditional Chinese medicine (TCM) syndrome (Zheng) in rheumatoid arthritis (RA) patients.METHODS:RA Patients were recruited in Guang'anmen Hospital,China Academy of Chinese Medical Sciences and in the Second Affiliated Hospital of Zhejiang Chinese Medical University,and diagnosed with a particular RA Zheng from their symptoms.Demographic characteristics,self-reported symptoms,and blood samples were collected from patients.All data were input into EpiData and analyzed using SPSS software.RESULTS:The study included 302 RA patients (age range:18-86 years).All patients were Chinese,and 85.1% were women.Cold and fatigue triggers were reported by 8.6% of patients,followed by triggers such as childbirth (4.3%),cold (3.0%),dampness (2.0%),menopause (1.3%),and psychentonia (0.7%).The most prevalent Zheng was dampness and heat blockage (Shire Yuzu in Chinese,SRYZ),diagnosed in 39.4% of patients (119),followed by phlegm and stagnation blockage (Tanyu Bizu,TYBZ) in 21.5%,liver and kidney deficiency (Ganshen Buzu,GSBZ) in 18.5%,dual deficiency of Qi and blood (Qixue Liangxu,QXLX) in 9.6%,cold and dampness blockage (Hanshi Bizu,HSBZ) in 6%,and wind and dampness blockage (Fengshi Bizu,FSBZ) in 5%.Increased length of time since RA diagnosis was associated with the GSBZ group.Patients diagnosed with the SRYZ Zheng had the highest disease activity score.Patients diagnosed with the QXLX Zheng had the lowest blood platelet counts;patients diagnosed with the QXLX and HSBZ Zhengs had lower C-reactive protein levels and lower health assessment questionnaire scores.Patients diagnosed with the GSBZ and QXLX Zhengs had the highest health assessment questionnaire scores.CONCLUSION:The specific Zheng was related to RA characteristics.The findings suggest that eliminating dampness,cooling the patient,and promoting blood circulation may assist in treating severe RA.

关键词： Arthritis,rheumatoid Symptoms and signs Syndrome complex Cross-sectional studies

Chinese registry of rheumatoid arthritis(CREDIT)V:sex impacts rheumatoid arthritis in Chinese patients

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Chinese Medical Journal 2022年第18期135卷 2210-2217页

作者： Nan Jiang Qin Li Hongbin Li Yongfei Fang Lijun Wu Xinwang Duan Jian Xu Cheng Zhao Zhenyu Jiang Yanhong Wang Qian Wang Xiaomei Leng Mengtao Li Xinping Tian Xiaofeng Zeng CREDIT Co-Authors Department of rheumatology and Clinical Immunology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science and TechnologyState Key Laboratory of Complex Severe and Rare DiseasesKey Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China Department of rheumatology the First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China Department of rheumatology the Affiliated Hospital of Inner Mongolia Medical CollegeHohhotInner Mongolia 010050China Department of rheumatology Southwest HospitalThird Military Medical UniversityChongqing 400038China Department of rheumatology and Immunology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China Department of rheumatology The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Department of rheumatology and Immunology First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China Department of rheumatology The First Affiliated Hospital of Guangxi Medical UniversityManningGuangxi 530021China Department of rheumatology The First Hospital of Jilin UniversityChangchunJilin 130021China Department of Epidemiology and Bio-Statistics Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China. 不详

Background: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.Methods: Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.Results: A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0vs. 6.7 mg/L), pain visual analogue scale (4.8vs. 4.5), patient’s and physician’s global assessment (4.9vs. 4.5 and 4.9vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3vs. 4.0) simplified disease activity index (21.9vs. 19.9), and clinical disease activity index (19.3vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4%vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.Conclusions: In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

关键词： Rheumatoid arthritis Sex Disease activity Treatment target Comorbidities