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PERIPHERAL BLOOD CD34^+ CELL MOBILIZATION IN 42 PATIENTS WITH SEVERE autoimmune disease

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Chinese Medical Sciences Journal 2007年第2期22卷 108-112页

作者： Wei Zhang Dao-bin Zhou Yan Zhao Jun-ling Zhuang Xiao-mei Leng Shu-jie Wang Li Jiao Fu-lin Tang Jie-ping Zhang Xuan Wang Ti Shen Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100730 Department of Rheumatology Peking Union Medical College HospitalChinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100730

Objective To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease. Methods Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2 +recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 μg·kg-1·d-1. The positive selection of CD34+ cell was performed through the CliniMACS. Results In 8.1±2.3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7±1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95×109/L and 0.035×109/L, respectively. After 2.4±0.6 times of leukapheresis, there gained 4.46×108/kg of MNC and 5.26×106/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (Pautoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

关键词： autoimmune disease CD34^+ cell mobilization

Role of myeloid-derived suppressor cells in autoimmune disease

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World Journal of Immunology 2014年第1期4卷 26-33页

作者： Kristen R Crook Peng Liu Department of Medicine Thurston Arthritis Research Center School of Medicine University of North Carolina at Chapel Hill Chapel Hill NC 27599 United States

Myeloid-derived suppressor cells(MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-basedcell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy.

关键词： Myeloid-derived suppressor cells autoimmune disease Autoimmunity T cells Chronic inflammation Immune regulation

The Landscape of peripheral T cell receptor repertoire in autoimmune disease

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The Landscape of peripheral T cell receptor repertoire in au...

Pharmacological insights into autophagy modulation in autoimmune diseases

第十二届全国免疫学学术大会

作者： LIU Xiao LU Qianjin Zhang Wei Zhao Ming BGI-Shenzhen Hunan Key Laboratory of Medical Epigenomics the second Xiangya HospitalCentral South University

The pathogenesis of autoimmune disease,represented by systemic lupus erythematosus(SLE)and rheumatoid arthritis(RA),is thought to involve the auto-reactivity of circulating and tissue-resident T *** studies have been ... 详细信息

关键词： T cell receptor autoimmune disease

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3364-3378页

作者： Ming-Yue Wu Er-Jin Wang Du Feng Min Li Richard D.Ye Jia-Hong Lu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 9999078China Key Laboratory of Protein Modification and Degradation State Key Laboratory of Respiratory DiseaseCollege of Basic Medical ScienceGuangzhou Medical UniversityGuangzhou 510000China School of Pharmaceutical Sciences National and Local United Engineering Lab of Druggability and New Drugs EvaluationGuangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510000China Kobilka Institute of Innovative Drug Discovery School of Life and Health Sciencesthe Chinese University of Hong KongShenzhen 518000China

As a cellular bulk degradation and survival mechanism,autophagy is implicated in diverse biological ***-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus(SLE)and inflammatory bowel disease(IBD),indicating that autophagy dysregulation may be involved in the development of autoimmune diseases.A series of autophagy modulators have displayed protective effects on autoimmune disease models,highlighting the emerging role of autophagy modulators in treating autoimmune *** review explores the roles of autophagy in the autoimmune diseases,with emphasis on four major autoimmune diseases[SLE,rheumatoid arthritis(RA),IBD,and experimental autoimmune encephalomyelitis(EAE)].More importantly,the therapeutic potentials of small molecular autophagy modulators(including autophagy inducers and inhibitors)on autoimmune diseases are comprehensively analyzed.

关键词： Autophagy autoimmune disease Systemic lupus erythematosus Inflammatory bowel disease Rheumatoid arthritis Experimental autoimmune encephalomyelitis Autophagy inducer Autophagy inhibitor

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

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Journal of Pharmaceutical Analysis 2023年第6期13卷 545-562页

作者： Jiuping Zeng Mingxing Li Qianyun Zhao Meijuan Chen Long Zhao Shulin Wei Huan Yang Yueshui Zhao Anqi Wang Jing Shen Fukuan Du Yu Chen Shuai Deng Fang Wang Zhuo Zhang Zhi Li Tiangang Wang Shengpeng Wang Zhangang Xiao Xu Wu Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Cell Therapy&Cell Drugs of Luzhou Key Laboratory LuzhouSichuan646000China South Sichuan Institute of Translational Medicine LuzhouSichuan646000China Department of Spleen and Stomach diseases The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouSichuan646000China School of Medicine Chengdu UniversityChengdu610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan646000China

As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune *** emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 *** RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding *** of small-molecule inhibitors have entered clinical ***,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was ***,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical *** limitations of current development in this area were also discussed to facilitate future research.

关键词： T helper 17 RORγt Small-molecule inhibitor Inflammatory disease autoimmune disease

The five major autoimmune diseases increase the risk of cancer:epidemiological data froma large-scale cohort study in China

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Cancer Communications 2022年第5期42卷 435-446页

作者： Ziyue Zhou Huazhen Liu Yiying Yang Jingya Zhou Lidan Zhao Hua Chen Yunyun Fei Wen Zhang Mengtao Li Yan Zhao Xiaofeng Zeng Fengchun Zhang Huaxia Yang Xuan Zhang Department of Rheumatology and Clinical Immunology National Clinical Research Center for Dermatologic and Immunologic Diseasesthe Ministry of Education Key LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Clinical Immunology Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Department of Medical Records Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China State Key Laboratory of Difficult Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China Department of Rheumatology National Center of GerontologyInstitute of Geriatric MedicineBeijing HospitalPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730P.R.China

Background:Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases(AIDs).This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese ***:A total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed-up for 38,726.55 patient-years,including those with systemic lupus erythematosus(SLE),rheumatoid arthritis(RA),Sjoren’s syndrome(SS),systemic scleroderma(SSc),and idiopathic inflammatory myositis(IIM).Demographic data,cancer incidence,predilecting sites and cancer onset time were recorded and compared among the five ***:Four hundred and thirty(5.3%)patients developed *** median agewas 57.5 years and AID durationwas 79.8 *** estimated total standardized incidence ratio(SIR)of cancer in AIDs patients was 3.37,with the highest SIR observed in IIM(4.31),followed by RA(3.99),SSc(3.77),SS(2.88)and SLE(2.58).The increased SIR of cancers in AID patients showed a female predominance(female ***:3.59 vs.2.77)and younger patient involvement(age<50 vs.≥50 years:4.88 vs.3.04).Patientswith SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder,corpus uteri and cervix *** with SS had a significantly high SIR for developing non-Hodgkin’s *** 3 years of IIM diagnosis,74.6%of the patients developed cancer and they had a high risk of ovarian *** was associated with a wide distribution of scancers,including non-Hodgkin’s lymphoma,gynecologic,urinary tract,thyroid gland and lung *** patients had increased SIRs for developing cervical uterine,lung,and breast ***:Patients with five major AIDs in China had an increased risk of developing cancer,with a predominance in women and younger patients,although cancer incidence,predilection site

关键词： autoimmune disease cancer risk standardized incidence ratio lupus erythematosus rheumatoid arthritis Sjoren’s syndrome systemic scleroderma idiopathic inflammatory myositis epidemiology

Cross-Reaction of SARS-CoV Antigen with Autoantibodies in autoimmune diseases

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Cellular & Molecular Immunology 2004年第4期1卷 304-307页

作者： YunshanWang ShanhuiSun HongShen LihuaJiang MaoxiuZhang DongjieXiao YangLiu XiaoliMa YongZhang NongjianGuo TanghongJia CentralLaboratory JinanCentralHospitalClinicalMedicalCollegeofShandongUniversityJinanChina. ShandongResearchCenterforTransplantationandTissueEngineering JinanChina.

To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody,detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates,in non-SARS subjects, 114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were *** results of ELISA showed that among 114 sera from healthy controls,4 (3.5%) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody;the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%,but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%.In 58 cases with SLE,positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58),respectively,in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies;in 10 cases with SS,positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10);in 16 cases with MCTD,positive rate of SARS-CoV-IgG was 37.5% (6/16),positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16);in 20 cases with RA,one case was positive (5%) of ***,of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls,SARS-CoV RNA and antibodies were all negative by RT-PCR and *** sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells *** studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls,and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS *** & Molecular Immunology.2004;1(4): 304-307.

关键词： SARS-CoV autoimmune disease cross-reaction

Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases:Current evidence

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World Journal of Diabetes 2021年第9期12卷 1426-1441页

作者： Ayan Roy Jayaprakash Sahoo Niya Narayanan Chandhana Merugu Sadishkumar Kamalanathan Dukhabandhu Naik Department of Endocrinology and Metabolism All India Institute of Medical SciencesJodhpur 342005India Department of Endocrinology Jawaharlal Institute of Postgraduate Medical Education and ResearchPuducherry 605006India

Dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 *** DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological ***-4 regulates several immune functions,including T-cell activation,macrophage function,and secretion of *** have reported an increase in autoimmune diseases like bullous pemphigoid,inflammatory bowel disease,and arthritis with DPP-4i *** relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more *** a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious ***,a heightened awareness from the clinicians is required to identify and treat any such *** this review,we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

关键词： autoimmune disease Bullous pemphigoid Diabetes Dipeptidyl peptidase-4 inhibitors Gliptins Inflammation

Advances in the role of helper T cells in autoimmune diseases

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Chinese Medical Journal 2020年第8期133卷 968-974页

作者： Xiao-Mei Zhang Chun-Yan Liu Zong-Hong Shao Department of Hematology Tianjin Medical University General HospitalTianjin 300052China

autoimmune diseases are primary immune diseases in which autoreactive antibodies or sensitized lymphocytes destroy and damage tissue and cellular components, resulting in tissue damage and organ dysfunction. Helper T cells may be involved in the pathogenesis of autoimmune diseases under certain conditions. This review summarizes recent research on the role of helper T cells in autoimmune diseases from two aspects, helper T cell-mediated production of autoantibodies by B cells and helper T cell-induced activation of abnormal lymphocytes, and provides ideas for the treatment of autoimmune diseases. The abnormal expression of helper T cells promotes the differentiation of B cells that produce autoantibodies, which leads to the development of different diseases. Among them, abnormal expression of Th2 cells and T follicular helper cells is more likely to cause antibody-mediated autoimmune diseases. In addition, abnormal activation of helper T cells also mediates autoimmune diseases through the production of abnormal cytokines and chemokines. Helper T cells play an essential role in the pathogenesis of autoimmune diseases, and a full understanding of their role in autoimmune diseases is helpful for providing ideas for the treatment of autoimmune diseases.

关键词： Helper T cells B cells autoimmune disease