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Altered influenza virus haemagglutinin(HA)-derived peptide is potent therapy for CIA by inducing Th1 to Th2 shift

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Cellular & Molecular immunology 2011年第4期8卷 348-358页

作者： Jian Sun Yuan Jia Ru Li Jianping Guo Xiaolin Sun Yanying Liu Yingni Li Haihong Yao Xia Liu Jing Zhao Zhanguo Li Department of rheumatology and immunology Clinical Immunology CenterPeking University People’s HospitalBeijingChina

There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune *** we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin(HA)-derived peptide in collagen-induced arthritis(CIA).CIA was induced in DBA/1 mice by immunisation with type II collagen(CII).Altered HA308-317,wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis *** and histological scores were assessed,and cytokine levels in the serum or supernatants from splenocytes were *** percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in *** results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated *** therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon(IFN)-c,interleukin(IL)-6,monocyte chemoattractant protein(MCP)-1,anti-CII IgG,IgG1 and IgG2a antibodies,and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 *** percentage of Th2(CD41IL-41)cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1(T helper 1;CD41INF-c1)cells both in vivo and in *** findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis(RA)treatment.

关键词： altered HA peptide collagen-induced arthritis Th1/Th2

IL-1β limits the extent of human 6-sulfo LacNAc dendritic cell (slanDC)-mediated NK cell activation and regulates CD95-induced apoptosis

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Cellular & Molecular immunology 2017年第12期14卷 976-985页

作者： Dejene Milkessa Tufa Fareed Ahmad Debanjana Chatterjee Gerrit Ahrenstorf Reinhold Ernst Schmidt Roland Jacobs Department of clinical immunology and rheumatology Hannover Medical School30625 HannoverGermany

To function optimally,human blood natural killer(NK)cells need to communicate with other immune ***,it has been shown that NK cells communicate with 6-sulfo LacNAc dendritic cells(slanDCs),which are able to stimulate NK cells in *** this study,we investigated how slanDCs regulate the level of NK cell *** secretion of interleukin(IL)-1βby slanDCs during coculture with NK cells increased as a result of signaling via intercellular adhesion molecule-1 on slanDCs following its interaction with lymphocyte functionassociated antigen-1 on NK ***-1βinduced the expression of Fas receptor(CD95)on NK *** binding of Fas ligand(CD178)to CD95 induced the apoptosis of activated NK ***,IL-1βalso induced increased cyclooxygenase-2 expression in slanDCs,which in turn enabled the cells to secrete prostaglandin(PG)-***,PGE2 acted as a suppressing agent,tuning down the activation level of NK *** summary,IL-1βlimits the level of NK cell activation by inducing apoptosis and suppression as a homeostatic regulatory function.

关键词： COX-2 Fas-induced apoptosis immunosuppression NK cells slanDCs

clinical heterogeneity of NLRP12-associated autoinflammatory diseases

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Genes & Diseases 2023年第3期10卷 1090-1100页

作者： Yue Li Mengyue Deng Yulu Li Xiaolan Mao Shi Yan Xuemei Tang Huawei Mao Department of rheumatology and immunology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Infection and ImmunityChongqing 400014China Department of rheumatology and immunology Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.

关键词： Autoinflammatory diseases Fanilial cold autoinflammatory syndr ome type 2(FCAS2) NLRP12-Associated autoinflammatory disease(NLRP12-AID) Nod-like receptor family pyrin domain-containing protein 12(NLRP12) Nuclear factor-Kappa B(NF-kB)

Autoimmune pancreatitis:current concepts

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Science China(Life Sciences) 2013年第3期56卷 246-253页

作者： WANG Qian ZHANG Xuan ZHANG FengChun Department of rheumatology and clinical immunology Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeKey Laboratory of Rheumatology and Clinical ImmunologyMinistry of Education

Autoimmune pancreatitis （AIP） is a distinct type of chronic pancreatitis with unique clinical, pathological, serological, and imaging features. AIP usually presents with obstructive jaundice. Imaging studies often reveal enlargement of the pancreas with a pancreatic mass and strictures of the main pancreatic duct. Two subtypes of AIP have recently been identified. Type 1 AIP is more prevalent in elderly Asian males and is characterized by lymphoplasmacytic sclerosing pancreatitis, obliterative phlebitis, and infiltration of large numbers of IgG4-positive plasma cells. Type II AIP is more prevalent in Caucasians and is characterized by granulocyte epithelial lesions. Most patients with type I AIP have a significantly elevated serum IgG4 con- centration, which is an important feature for diagnosis and for differentiating between AIP and other conditions such as pan- creatic cancer. Extrapancreatic complications are common, such as sclerosing cholangitis, sclerosing sialadenitis, retroperito- neal fibrosis in type I AIP, and ulcerative colitis in type II AIP. A rapid response to glucocorticoids treatment is suggestive of AlP, but the relapse rate is high, warranting the use of immunosuppressant treatment. B-cell depletion with rituximab may be a promising therapy. The prognosis of AIP is generally benign if treated promptly, and spontaneous remission occurs in a pro- portion of patients.

关键词： autoimmune pancreatitis IgG4 pancreatic cancer glucocorticoids

Exploring pathogenesis of primary biliary cholangitis by proteomics: A pilot study

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World Journal of Gastroenterology 2017年第48期23卷 8489-8499页

作者： Chui-Wen Deng Li Wang Yun-Yun Fei Chao-Jun Hu Yun-Jiao Yang Lin-Yi Peng Xiao-Feng Zeng Feng-Chun Zhang Yong-Zhe Li Department of rheumatology and clinical immunology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College Key Laboratory of rheumatology and clinical immunology Ministry of Education

AIM To explore the pathogenesis of primary biliary cholangitis(PBC) by identifying candidate autoantibodies in serum samples by proteomics and *** Nine antimitochondrial antibody(AMA)-positive PBC patients and nine age-and sex-matched AMA-negative PBC patients were recruited. Antigen enrichment technology was applied to capture autoantigens of human intrahepatic biliary epithelial cells(Hi BECs) that are recognized by autoantibodies from the sera of PBC patients. Candidate autoantigens were identified by label-free mass spectrometry. Bioinformatics analysis with Max Quant software(version 1.***.2.8),DAVID platform,and Cytoscape v.3.0 allowed illustration of pathways potentially involved in the pathogenesis of *** In total,1081 candidate autoantigen proteins were identified from the PBC patient pool. Among them,371 were determined to be significantly differentially expressed between AMA-positive and-negative PBC patients(P < 0.05). Fisher's exact test was performed for enrichment analysis of Gene Ontology protein annotations(biological processes,cellular components,and molecular functions) and the Kyoto Encyclopedia of Genes and Genomes pathways. Significantly different protein categories were revealed between AMA-positive and-negative PBC patients. As expected,autoantigens related to mitochondria were highly enriched in AMApositive PBC patients. However,lower levels of AMA were also detected in AMA-negative PBC patients. In addition,autoantigens of AMA-negative PBC patients were mainly involved in B-cell activation,recognition of phagocytosis,and complement *** AMA-negative PBC individuals may not exist,but rather,those patients exhibit pathogenesis pathways different from those of AMA-positive PBC. Comprehensive research is needed to confirm these observations.

关键词： Anti-mitochondrial antibody Bioinformatics Pathogenesis Primary biliary cholangitis Proteomics

New insights into the fascinating world of glucocorticoids:the dexamethasone-miR-342-Rictor axis in regulatory T cells

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Cellular & Molecular immunology 2021年第3期18卷 520-522页

作者： Frank Buttgereit Timo Gaber Department of rheumatology and clinical immunology Charity University MedicineBerlinGermany

In a recent issue of Immunity,Kim et *** previously unknown effects of glucocorticoids on murine regulatory T(Treg)cells,and this report added another very interesting perspective to the already very diverse body of knowledge about these important hormones and therapeutics compared to the body of knowledge about other clinically used drugs.1 Treg cells are important regulators of the immune response in autoimmune and allergic inflammation.

关键词： drugs allergic

clinical heterogeneity and five phenotypes identified in pediatric Behçet’s syndrome: a cohort study from Shanghai Behçet’s syndrome database

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World Journal of Pediatrics 2024年第8期20卷 801-808页

作者： Dan Hu Chun-Hui She Hua-Fang Bao Jun Zou Jian-Fei Cai Jing‑Fen Ye Yan Shen Hai‑Fen Ma Dan Luo Jian-Long Guan Department of rheumatology and immunology Huadong Hospital Affiliated to Fudan University221 Yan’an West Road200040ShanghaiChina

Objectives Behçet’s syndrome(BS)is a rare disease of unknown etiology,with limited reports especially in pediatric *** clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this *** A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and *** analysis was then performed to identify the phenotypes of pediatric *** A total of 2082 BS patients were included in this study,1834 adults and 248 *** with adult-onset BS,pediatric BS had a higher incidence of folliculitis[relative risks(RR)and 95%confidence interval(CI)1.3(1.0–1.5)],uveitis of the left eye[RR and 95%CI 2.3(1.0–5.0)],intestinal ulcer complications[RR and 95%CI 2.1(1.1–4.2)],pericarditis[RR and 95%CI 2.5(1.0–6.2)],and psychiatric disorders[RR and 95%CI 2.8(1.0–7.9)],while the incidence of thrombocytopenia was lower[RR 0.2(0.1–1.0)].Among pediatric BS,females had more genital ulcers,while males were more likely to have skin lesions,panuveitis,vascular involvement,venous lesions,cardiac involvement,and aortic *** analysis classified pediatric BS into five clusters(C1–C5):C1(n=61,24.6%)showed gastrointestinal(GI)involvement;C2(n=44,17.7%)was the central nervous system(CNS)type where 23 cases overlapped joint involvement;in C3(n=35,14.1%),all patients presented with arthritis or arthralgia;all patients in C4(n=29,11.7%)manifested ocular involvement,with a few patients overlapping with GI involvement or joint damage;C5(n=79,31.9%)was the mucocutaneous type,presenting both oral ulcers,genital ulcers,and skin *** The clinical features of pediatric and adult BS differ *** and female pediatric BS also have a distinct *** phenotypes including GI,CNS,joint,ocular,and mucocutaneous types were identified for pediatric BS.

关键词： Behçet's syndrome clinical manifestation Cluster analysis Pediatric Phenotype

Risk factors for hepatic decompensation in patients with primary biliary cirrhosis

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World Journal of Gastroenterology 2013年第7期19卷 1111-1118页

作者： Tian-Yan Shi Li-Na Zhang Hua Chen Li Wang Min Shen Xuan Zhang Feng-Chun Zhang Department of rheumatology Key Laboratory of Rheumatology and Clinical ImmunologyPeking Union Medical College HospitalChinese Academy of Medical Science

AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) ***:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were *** signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during *** regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and ***:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were *** hundred and forty-five(93.5%) were seropositive for anti-mitochondrial *** presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune *** the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 *** cumulative survival rate and median survival time were 83.9% and 181.7 mo,*** regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P clinical features and survival of PBC in China are consistent with those described in Western ***:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histolog

关键词： Primary biliary cirrhosis Risk factor Hepatic decompensation Survival Ursodeoxycholic acid response Anti-centromere antibodies Histological stage

Juvenile dermatomyositis:advances in clinical presentation,myositis-specific antibodies and treatment

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World Journal of Pediatrics 2020年第1期16卷 31-43页

作者： Jian-Qiang Wu Mei-Ping Lu Ann M.Reed Department of rheumatology immunology and Allergy Children's HospitalZhejiang University School of MedicineHangzhou 310052China Department of Pediatrics Division of Pediatric RheumatologyDuke University School of MedicineDurham 27710USA

Background Juvenile dermatomyositis(JDM)is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin,muscle and vital *** the clinical features and treatment of JDM have not been fully *** sources Databases underwent through PubMed for articles about the clinical features,myositis-specific antibodiesof JDM and its treatment,and we selected publications written in English which were relevant to the topic of this *** clinical features and myositis-specific antibodies may predict the severity and prognosis of *** the mortality rate has been lower with traditional treatments,such as corticosteroid,intravenous immunoglobulin,and diseasemodifying anti-rheumatic drugs such as methotrexate,their usages are *** biological therapies seem to be effective for refractory JDM patients,but more clinical trials are *** JDM is a sever disease of *** need to better understand recent advances of JDM in the context of clinical features including skin manifestations,muscle weakness and organ damage,myositis-specific antibodies and their associated outcomes and the treatment of disease.

关键词： Biologic agents Extramuscular manifestations Juvenile dermatomyositis Myositis autoantibodies