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A citrullinated antigenic vaccine in treatment of autoimmune arthritis

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Science Bulletin 2024年第18期69卷 2920-2929页

作者： Xu Jin Tianya Dong Qian Wang Yang Xie Xiangyu Fang Chaonan Wei Shuyan Liu Xi Zheng Ping Wang Danxue Zhu Lulu Cao Suwei Dong Kechi Fang Chao Zhong Jing Wang fanlei hu Zhanguo Li Department of Rheumatology and Immunology Peking University People’s Hospital&Beijing Key Laboratory for Rheumatism Mechanism and Immune DiagnosisBeijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100049China Department of Chemical Biology School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Institute of Systems Biomedicine Department of ImmunologyNHC Key Laboratory of Medical Immunology(Peking University)Beijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China

Rheumatoid arthritis(RA)is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk *** has been shown that antigen-specific targeting could be a promising therapeutical strategy for RA by restoring immune tolerance to self-antigens without compromising normal *** of antigens enhances antigenic properties and induces autoimmune ***,we showed that citrullinated antigenic(citAg)vaccine ameliorated collageninduced arthritis with decreased T-helper 1(Th1)and Th17 cells,downregulated proinflammatory cytokines including interlukin-6 and tumor necrosis factor-a,and inhibited antigen recall responses.B cell receptor sequencing further revealed that citAg vaccine could dampen the dysregulated V(D)J recombination,restoring the immune *** together,the results demonstrated that citAg vaccine might have a therapeutic effect on RA.

关键词： CitAg Citrullination Collagen typeⅡ Therapeutic vaccine Immune tolerance Rheumatoid arthritis

三级甲等医疗机构个人科技量值评价体系的构建与应用

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中华医学科研管理杂志 2024年第2期37卷 103-107页

作者：李媛梁公文胡凡磊申占龙赵翔宇北京大学人民医院北京100044

目的探索建立适用于三级甲等医疗机构科技人才的个人科技量值评价体系。方法运用文献调研,结合医疗机构科技评价指标与实践,构建医疗机构个人科技量值评价基本框架。采用德尔菲法筛选指标,采用专家赋值法确定指标系数。采用专家评价法... 详细信息

目的探索建立适用于三级甲等医疗机构科技人才的个人科技量值评价体系。方法运用文献调研,结合医疗机构科技评价指标与实践,构建医疗机构个人科技量值评价基本框架。采用德尔菲法筛选指标,采用专家赋值法确定指标系数。采用专家评价法进行内容效度检验。结果构建由科研产出、学术影响、科研条件和学术诚信4个一级指标、6个二级指标和13个三级指标构成的个人科技量值指标体系。各级指标的内容效度指数I-CVI的值为0.83至1,指标总体内容效度指数S-CVI=0.96。应用于医疗机构科技人才的职称评审和人才项目的遴选及跟踪评价。结论个人科技量值评价体系导向高质量科技创新和人才的能力与贡献,为推进科技人才评价改革试点工作提供评价工具。

关键词：医疗机构科技人才评价科技量值德尔菲法专家赋值法

The role of human ADA2a in the regulation of p53 acetylation and stability

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Chinese Science Bulletin 2011年第4期56卷 397-405页

作者： huANG Jing ZHANG Li XIAO Lin XU LanJun hu fanlei SHAO WenWei LIU Wei MO XiaoNing SHI TaiPing QIU XiaoYan Laboratory of Medical Immunology School of Basic Medical Science Peking University Health Science Center Beijing 100191 China Chinese National human Genome Center Beijing 100176 China

The tumor suppressor protein p53 is a well-known transcription factor that functions as a critical component of the genotoxic stress response via regulating the expression of effector proteins that control cellular fate following DNA damage. The human p300/CBP-associated factor(PCAF)-containing histone acetyltransferase(HAT) complex is important for the stability and activity of p53 via its acetylation. The human homolog of yeast alteration/deficiency in activation 2a(ADA2a) is a stable component of the human PCAF-containing HAT complex. In this study,we demonstrated that p53 and hADA2a physically interact with each other in human HEK 293T cells. Using overexpression and small interfering RNA-mediated knockdown,we demonstrated that hADA2a stabilizes p53 via promoting its acetylation at lysine 320 - a PCAF-dependent acetylation site. Furthermore,hADA2a can potentiate the transcriptional activity of p53 at the BAX and p21 promoters to induce cell apoptosis and cell cycle arrest. Overall,our results establish that hADA2a,a component of the PCAF-containing histone acetyltransferase co-activator complex,is a mediator of acetylation-dependent stabilization and activation of p53 in mammalian cells.

关键词： p53基因乙酰化稳定人类调节作用组蛋白乙酰转移酶细胞周期阻滞转录因子

Pathogenic conversion of regulatory B10 cells into osteoclastpriming cells in rheumatoid arthritis

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Pathogenic conversion of regulatory B10 cells into osteoclas...

第十一届全国免疫学学术大会

作者： hu fanlei Liu Hongjiang Jia Yuan Li Zhanguo Department of Rheumatology and Immunology Peking University People’s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135)

Objectives:Regulatory B10 cells were functionally impaired in rheumatoid arthritis(RA),yet the mechanisms were unclear.B cells are recently recognized as important participants in osteoclastogenesis by producing *** t... 详细信息

关键词： Rheumatoid arthritis regulatory B10 cells osteoclasts RANKL

Impaired CD27+IgD+ B cells with altered gene signature in rheumatoid arthritis

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Impaired CD27+IgD+ B cells with altered gene signature in rh...

第十三届全国免疫学学术大会

作者： fanlei hu Wei Zhang Yongfu Wang Zhanguo Li Peking University People's Hospital First Hospital Affiliated to Baotou Medical College

Natural antibodies, particularly natural IgM, are proved to play indispensable roles in the immune defenses against common infections. More recently, the protective roles of these natural IgM were also recognized in autoimmune diseases. They are mainly produced by B-1 and innate-like B cells(ILBs). human CD19CD27IgD B cells, also termed as unswitched memory B cells, were proposed to be a kind of ILBs. However, functional features and characteristics of these cells in rheumatoid arthritis(RA) remained poorly understood. In this study, we found that human CD27IgD B cells could produce natural antibody-like IgM. Under RA circumstance, the frequencies of these cells were significantly decreased. Moreover, the IgM-producing capacities of these cells were also dampened. Interestingly, the BCR repertoire of these cells was altered in RA, demonstrating decreased diversity with preferential usage alteration from VH3-23 D to VH1-8. Single cell sequencing further revealed the proinflammatory biased features of these cells in RA. These CD27IgD B cells were negatively correlated with RA patient disease activities and clinical manifestations. After effective therapy with disease remission in RA, these cells could be recovered. Taken together, these results have revealed that CD27IgD B cells were impaired in RA with dysfunctional features, which might contribute to the disease perpetuation.

关键词： rheumatoid arthritis innate-like B cells CD27+IgD+ B cells natural IgM gene signature

SR-A neutralizing antibody attenuates osteoclastogenesis in rheumatoid arthritis

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SR-A neutralizing antibody attenuates osteoclastogenesis in ...

第十四届全国免疫学学术大会

作者： Yang Xie Xiang Jiang Ping Wang Xi Zheng Zhanguo Li fanlei hu Peking University People's Hospital 北京大学

Rheumatoid arthritis(RA) is an autoimmune disease characterized by proliferative synovitis with deterioration of bone and *** are the active participants in bone destruction of *** with great advances,most current therapeutic strategies for RA have limited effects on bone *** scavenger receptor A(SRA) is a class of pattern recognition receptors(PRRs) involved in bone metabolism and osteoclast ***,we demonstrated that serum SR-A levels were positively correlated with bone destruction in RA ***-SR-A neutralizing antibodies significantly ameliorated osteoclast differentiation in vitro both in RA patients and collagen-induced arthritis(CIA) ***,anti-SR-A neutralizing antibody could inhibit osteoclast formation in CIA mice in vivo,exhibiting promising protective *** results suggest that blockade of SR-A by anti-SR-A neutralizing antibodies might provide a potential therapeutic strategy for bone destruction in RA.

关键词： Rheumatoid arthritis scavenger-receptor A osteoclast

Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study

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Scavenger receptor-A is a biomarker and effector of rheumato...

第十四届全国免疫学学术大会

作者： fanlei hu Xiang Jiang Yang Xie Xi Zheng Ping Wang Zhanguo Li Peking University People’s Hospital

Early diagnosis is critical to improve outcomes in rheumatoid arthritis(RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A(sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.

关键词： Rheumatoid arthritis biomarker scavenger receptor-A

FFA in synovial fluid is possibly related to the attack of acute gouty arthritis

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FFA in synovial fluid is possibly related to the attack of a...

第九届全国免疫学学术大会

作者： Li Zheng Chun Li fanlei hu Yingni Li Hongjiang Liu Xuewu Zhang Zhanguo Li Department of Rheumatology and Immunology Peking University People’s Hospital

Background:It is the excessive consumption of food or alcohol that elicits the inflammation of acute gout *** is also related to metabolic *** the mechanism of initiates flares of gout remains poorly ***:The aim of this study is to exam the concentration of FFA(free fat acid)in serum and SF(synovial fluid)of patients with gouty arthritis and hyperuricemia and to investigate the relationship between FFA and the attack of gouty ***:Forty-three patients with gouty arthritis(22 under acute attack and 21 during the intermission of attack),22patients with hyperuricemia and 23 healthy individuals were involved and the levels of FFA in serum were *** of FFA in SF were detected from 30 patients with gouty arthritis and 11 patients with OA(osteoarthritis).The levesl of FFA in both serum and SF were evaluated by ACS·ACOD ***:The circulating FFA in patients with acute gouty arthritis was remarkably higher than that in healthy controls(1.04±0.27 mEq/L VS 0.67±0.13 mEq/L,p<0.05),which was also significantly elevated compared to hyperuricemia patients(0.72±0.20 mEq/L,p<0.05)and gout patients in the intermission of attack(0.77±0.15 mEq/L,p<0.05).Level of FFA in SF in patients with acute gouty arthritis was considerably higher than that in patients with OA(0.34±0.03mEq/L VS 0.19±0.02 mEq/L,p<0.001).Conclusions:The circulating FFA was elevated in patients with acute gouty ***,the levesl of FFA in SF was much higher in patients with acute gouty arthritis,which was possibly related to the attack of acute gouty arthritis.

关键词： gouty arthritis hyperuricemia free fat acid synovial fluid

Macrophage Scavenger Receptor 1(Msrl) as a protein biomarker for the diagnosis of rheumatoid arthritis:a large-scale,multicenter study

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Macrophage Scavenger Receptor 1(Msrl) as a protein biomarker...

第十二届全国免疫学学术大会

作者： Jiang Xiang Li Yingni Du Yan Wu huaxiang Zhang Wei Wang Yongfu hu fanlei Li Zhanguo Department of Rheumatology &Immunology Peking University People's Hospital Department of Rheumatology & Immunology The Second Affiliated HospitalZhejiang University College of Medicine Department of Rheumatology & Immunology The First affiliated hospital of baotou Medical College

Objective:Previous work suggests that Msrl is involved in the pathogenesis of rheumatoid arthritis(RA).In our study,we assessed whether measurement of soluble Msrl in serum could be an independent diagnostic marker fo... 详细信息

关键词： rheumatoid arthritis biomarker sMsr1 diagnostic value