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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

Osteoimmunology: memorandum for rheumatologists

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Science China(Life Sciences) 2016年第12期59卷 1241-1258页

作者： Lidan Zhao Linfang Huang Xuan Zhang Department of rheumatology & Clinical Immunology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College the Ministry of Education Key Laboratory Department of rheumatology the First People's Hospital of Yueyang

Rapid progress has been made in exploring the connections between the skeletal system and the immune system over the past decade. Bone tissue forms developmental niches for hematopoietic stem cells, and activated immune cells are involved in bone metabolism regulation and are potent mediators of osteoporosis and bone erosion under pathological conditions. The interdisciplinary field of osteoimmunology has emerged to pool the knowledge of the interdependence of these two systems, including the shared ligands and receptors, their crosstalk and interaction, and common intracellular signaling pathways with bidirectional influence. The receptor activator of nuclear factor-kappa B(RANK)/RANK ligand(RANKL)/osteoprotegerin(OPG) triad is the key vinculum, with multifaceted potency, being not only essential for osteoclastogenesis but also critical for lymph node organogenesis and lymphopoiesis as well as for immune regulation. In this review, we summarize the progress in this area, focusing on those aspects of interest concerning rheumatic diseases.

关键词： osteoimmunology bone remodeling osteoclastogenesis immune cells RANKL

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

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World Journal of Gastroenterology 2005年第8期11卷 1091-1095页

作者： Timm Kirchhoff Lars Zender Sonja Merkesdal Bernd Frericks Nisar Malek Joerg Bleck Stefan Kubicka Stefan Baus Ajay Chavan Michael P.Manns Michael Galanski Department of Diagnostic Radiology Department of Gastroenterology Division of rheumatology Department of Radiology and Nuclear Medicine

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the ***: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and ***: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were *** responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 ***: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizati

关键词： Cholangiocellular carcinoma Gemcitabine Intraarterial chemoembolization

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

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats

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Chinese Journal of Integrative Medicine 2018年第4期24卷 278-283页

作者： SHEN Hong-bo HUO Ze-jun BAI Yun-jing HE Xiao-juan LI Chang-hong ZHAO Yu-kun GUO Qing-qing Department of Traditional Chinese Medicine Peking University Third Hospital Division of rheumatology PLA Army General Hospital Institute of Basic Research in Clinical Medicine Academy of Chinese Medical Sciences Division of rheumatology Peking University Third Hospital

Objective： To observe the effect of norcantharidin（NCTD） on collagen-induced arthritis（CIA） rats. Methods： Sixty Sprague-Dawley（SD） rats were randomly divided into 6 groups（n=10）： normal group, CIA model group（model group）, NCTD low-dose group [1.35 mg/（kg·d）], NCTD middle-dose group [2.7 mg/（kg·d）], NCTD high-dose group [5.4 mg/（kg·d）] and methotrexate（MTX） group [1.8 mg/（kg/w）]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin（H＆E） staining. The serum levels of interleukin（IL） 1β, IL-6, tumor necrosis factor（TNF）-α, vascular endothelial growth factor（VEGF）, IL-17 and transform growth factor（TGF） β were detected by enzyme linked immunosorbent assay（ELISA）. The mRNA expression of retinoid-related orphan nuclear receptor γ t（ROR γ t） and forkhead box P3（Foxp3） in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. Results： MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats＇ ankle joints compared with the model group（P〈0.05 or P〈0.01）. All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats（P〈0.05）. Only middle-and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats（P〈0.05）. However, NCTD has no effect on vascular endothelial growth factor（VEGF） level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group（P〈0.05）. The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group（P〈0.05）. Conclusion： NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.

关键词： norcantharidin collagen-induced arthritis cytokine Th17/Treg forkhead box P3 retinoid related orphan nuclear receptor γt

The regulation of the Treg/Th 17 balance by mesenchyma stem cells in human systemic lupus erythematosus

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Cellular & Molecular Immunology 2017年第5期14卷 423-431页

作者： Dandan Wang Saisai Huang Xinran Yuan Jun Liang Renju Xu Genhong Yao Xuebing Feng Lingyun Sun Department of rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing China

Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was not depended on cell-cell co

关键词： mesenchymal stem cells regulatory T cells systemic lupus erythematosus T helper 17 cells umbilical cord

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

Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

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World Journal of Gastroenterology 2021年第20期27卷 2657-2663页

作者： Hiroko Sato Tsuyoshi Shirai Hiroshi Fujii Tomonori Ishii Hideo Harigae Department of Hematology and rheumatology Tohoku University Graduate School of MedicineSendai 9808574Japan

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and ***,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been ***,the appropriate management of patients with CPA-associated severe enteritis is *** SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic *** received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/*** days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the *** testing revealed hypoalbuminemia,suggesting proteinlosing *** tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen *** and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 *** her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were *** supportive therapies improved her condition,and her enteritis gradually *** was finally discharged 7 mo *** Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

关键词： Antineutrophil cytoplasmic antibody Cyclophosphamide Enteritis Granulomatosis with polyangiitis Plasma exchange Vasculitis Case report