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Identification of differently expressed mRNAs by peripheral blood mononuclear cells in Vogt-Koyanagi-Harada disease

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Genes & Diseases 2022年第5期9卷 1378-1388页

作者： Yujing Li Guannan Su Fanfan Huang Ying Zhu Xiang Luo aize kijlstra Peizeng Yang The First Affiliated Hospital of Chongqing Medical University Chongqing Key Lab of OphthalmologyChongqing Eye InstituteChongqing 400016PR China University Eye Clinic Maastricht Maastricht 6211the Netherlands

Vogt-Koyanagi-Harada disease(VKH)is a rare autoimmune disease characterized by diffuse and bilateral uveitis,alopecia,tinnitus,hearing loss,vitiligo and *** transcriptional expression pattern of peripheral blood mononuclear cells(PBMC)in VKH remains largely *** this study,mRNA sequencing was conducted in PBMC from VKH patients with active uveitis before treatment(n=7),the same patients after prednisone combined with cyclosporine treatment(n=7)and healthy control subjects strictly matched with gender and age(n=7).We found 118 differentially expressed genes(DEGs)between VKH patients and healthy control subjects,and 21 DEGs between VKH patients before and after ***1 was selected as a potential biomarker to monitor the development of VKH according to the mRNA *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed to predict the possible biological functions and signaling pathways of *** degranulation,peptidase regulator activity,secretory granule membrane,cellular response to peptide,growth factor binding and cell projection membrane were enriched as GO annotations of *** acid metabolism and mitogen-activated protein kinase(MAPK)signaling pathway were potential signaling pathways involved in pathogenesis and drug response of VKH.A protein–protein interaction(PPI)network was constructed by STRING,and colony stimulating factor 1 receptor(CSF1R)was identified as the hubgene of all DEGs by *** cell type presumed to contribute to the aberrant expression of DEGs was analyzed with the use of publicly available single-cell sequencing data of PBMC from a healthy donor and single-cell sequencing dataset of monocytes from VKH *** findings may help to decipher the underlying cellular and molecular pathogenesis of VKH and may lead novel therapeutic applications.

关键词： Vogt-KoyanagiHarada disease uveitis mRNA sequencing Peripheral blood mononuclear cells

The genetics of Behcet’s disease in a Chinese population

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Frontiers of Medicine 2012年第4期6卷 354-359页

作者： Shengping Hou aize kijlstra Peizeng Yang The First Affiliated Hospital of Chongqing Medical University Chongqing 400016China Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology Chongqing 400016China University Eye Clinic Maastricht MaastrichtLimburgthe Netherlands

Behcet’s disease is defined as a multisystemic inflammatory *** the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s *** explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and *** associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,*** genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination *** findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.

关键词： Behcet’s disease SNPs immune gene genetic study

Immunohistochemical Studies of Macrophages and MHC Class Ⅱ -positive Cells in the Iris and Ciliary Body of Lewis Rats

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Eye Science 1996年第1期16卷 15-19页

作者： Alex F.de Vos aize kijlstra Netherlands Ophthalmic Research Institue Netherlands Ophthalmic Research Institue University of AmsterdamAmsterdamThe Netherlands

Purpose:To investigate the density, distribution and morphology of macrophages and MHC class II -positive dendritic cells in the iris and ciliary body of lewis rats. Methods:Immunohistochemistry was performed using monoclonal antibodies specific to monocytes and macrophages (ED1,ED2) and MHC class II -positive cells (OX6) on wholemounts of the iris-ciliary body complex isolated form normal lewis ***:A well developed network of macrophages was present in the iris and ciliary body of normal lewis rats. These cells, morphologically displaying dendriti-form or pleiomorphic appearance, were more densely arranged in mid-iris (950 + 189 cells/mm2) than in iris base (482 ± 78 cells/mm2) and pupil margin (595 ± 92 cells/mm2). A similar network of MHC class II -positive cells with a cell density 452 ± 78 cells/mm2 was almost uniformly distributed in the iris of normal lewis *** : A network of macrophages and MHC class II -positive cells was established in the iris and ciliary body of

关键词： wholemounts of iris-ciliary body macrophages MHC class Ⅱ-positive cells immunohistochemistry

TLR4-MyD88在大鼠急性前葡萄膜炎虹膜中的表达

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眼科研究 2010年第2期28卷 97-102页

作者：李上卢弘胡小凤陈巍杨培增 aize kijlstra 许颖知王婧首都医科大学附属北京朝阳医院眼科北京100020 北京海淀妇幼保健医院眼科 100080 重庆医科大学附属第一医院眼科 400016 马斯特里赫特眼科研究中心荷兰

目的观察内毒素诱导的大鼠急性前葡萄膜炎(EIU)虹膜组织内Toll样受体4(TLR4)、髓样分化因子88(MyD88)及核因子-κBp65(NF-κB p65)的表达。方法Wistar大鼠50只,随机分为5组,0、12、24、48、72h,每组10只,0h组为正常对照组,其余4组均足... 详细信息

目的观察内毒素诱导的大鼠急性前葡萄膜炎(EIU)虹膜组织内Toll样受体4(TLR4)、髓样分化因子88(MyD88)及核因子-κBp65(NF-κB p65)的表达。方法Wistar大鼠50只,随机分为5组,0、12、24、48、72h,每组10只,0h组为正常对照组,其余4组均足垫部注射霍乱弧菌内毒素脂多糖(LPS)200μg,建立EIU动物模型,每隔2h用裂隙灯观察大鼠眼前节炎症反应。通过铺片免疫组织化学染色,检测虹膜睫状体组织内TLR4、MyD88和NF-κBp65的表达,并对虹膜内TLR4+和MyD88+及NF-κBp65+细胞进行计数。结果注射后24～48h大鼠眼前段的炎症反应达到高峰,72h炎症反应逐渐缓解。组织病理学检查表明,虹膜睫状体组织的炎性细胞浸润在24～48h达到高峰,与临床反应结果相符。TLR4在模型鼠虹膜睫状体炎复合体中表达的免疫组织化学检测结果表明,0h组虹膜铺片内无阳性细胞,12h后可见细胞形态大多为类圆形的阳性细胞,48h达高峰,72h阳性细胞数开始减少,各组阳性细胞数总体差异有统计学意义(F=46.79,P<0.05)。MyD88和NF-κBp65的表达与TLR4的改变趋势相一致(F=54.37,P<0.05;F=85.32,P<0.05)。结论内毒素诱导的EIU虹膜内,TLR4及其下游信号传导分子的表达量发生改变,提示TLR4-MyD88依赖传导途径可能参与了EIU的发病。

关键词：内毒素葡萄膜炎 TLR4 MyD88 NF—κB p65

内毒素在Lewis鼠诱导的角膜改变——角膜平片的免疫组织化学研究

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Eye Science 1996年第2期16卷 70-74页

作者：杨培增 Alex F de Vos aize kijlstra 中山医科大学中山眼科中心卫生部眼科学实验室广州510060 荷兰国家眼科研究所

目的:探讨内毒素全身注射所致的角膜改变。方法:使用抗单核细胞、巨噬细胞和MHC-Ⅱ类抗原阳性细胞的单克隆抗体,用标准的ABC方法于内毒素注射前、后制备的角膜平片上进行免疫组织化学染色。结果:发现在正常角膜中央区实质内有散在分布... 详细信息

目的:探讨内毒素全身注射所致的角膜改变。方法:使用抗单核细胞、巨噬细胞和MHC-Ⅱ类抗原阳性细胞的单克隆抗体,用标准的ABC方法于内毒素注射前、后制备的角膜平片上进行免疫组织化学染色。结果:发现在正常角膜中央区实质内有散在分布的巨噬细胞,越近角膜缘分布越密集,MHC-Ⅱ类抗原阳性细胞则仅存在于角膜缘;内毒素注射后,中央区角膜单核巨噬细胞增多,这些细胞于角膜实质内发生了一系列形态学改变,MHC-Ⅱ类抗原阳性细胞仅见于注射后早期的中央区角膜内皮面。结论:内毒素诱导的角膜中巨噬细胞的增多可能是机体应激状态下的重要防御机制,角膜实质中MHC-Ⅱ类抗原的缺如则对维持角膜局部免疫微环境的稳定性有重要意义。眼科学报1996;12:70—74。

关键词：细菌内毒素角膜平片巨噬细胞 MHC-Ⅱ类抗原阳性细胞免疫组织化学

Role of T-cell receptor V beta 8.3 peptide vaccine in the prevention of experimental autoimmune uveoretinitis

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Chinese Medical Journal 2006年第9期119卷 740-748页

作者： ZHANG Rui YANG Pei-zeng WU Chang-you JIN Hao-li LI Bing HUANG Xiang-kun ZHOU Hong-yan GAO Yang ZHU Lian-xiang aize kijlstra Zhongshan Ophthalmic Centre Sun Yat-sen University Guangzhou 510060 China Department of Immunology Sun Yat-sen University Guangzhou 510089 China Division of Immunology Children＇s Hospital Boston Harvard Medical School Boston MA 02115 USA Animal Sciences Group Wageningen University and Research Centre Lelystad Eye Research Institute Maastricht and Department of Ophthalmology Academic Medical Centre University of Amsterdam the Netherlands

Background T-cell receptor （TCR） plays an important role in the development of autoimmune diseases. Recently, it was reported that immunization of animals with TCR peptide derived from the pathogenic cells could prevent autoimmune diseases. The aim of this study was to investigate whether vaccination with a synthetic peptide from the hypervariable region of TCR Vβ 8.3, an experimental autoimmune uveoretinitis （EAU）-associated gene, was able to prevent the disease. Methods EAU was induced in Lewis rats by immunization with IRBP R16 peptide emulsified in complete Freund＇s adjuvant （CFA）. The clinical and histological appearances were scored. Delayed type hypersensitivity （DTH） and lymphocyte proliferation were detected. Cytokine levels of aqueous humour, supernatants of cells from spleen and draining lymph nodes were measured by enzyme linked immunosorbent assay （ELISA）. Gene expression of TCR Vβ8.3 on CD4^＋ T cells was examined by real time quantitative polymerase chain reaction （PCR）. Results After vaccination, the intraocular inflammation was significantly mitigated, antigen specific DTH and lymphocyte proliferation responses were suppressed, interleukin （IL）-2 in aqueous humour, interferon （IFN）-γ and IL-2 produced by the spleen and draining lymph node cells were significantly decreased, whereas the production of IL-4 and IL-10 were increased. The response of draining lymph node cells to TCR Vβ 8.3 peptide was enhanced after vaccination. Inoculation with CFA alone did not affect the severity of EAU and the above parameters. The suppression of EAU was much stronger in the group of four fold inoculations than the group of two fold inoculations. The expression of TCR Vβ 8.3 gene was significantly reduced in the group of fourfold inoculations. Conclusion Vaccination with the synthetic TCR Vβ 8.3 peptide could remarkably inhibit the development of EAU.

关键词： uveoretinitis autoimmune T-cell receptor peptide vaccine

FAS gene copy numbers are associated with susceptibility to Behcet's disease and VKH syndrome in Han Chinese

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FAS gene copy numbers are associated with susceptibility to ...

内毒素诱导大鼠葡萄膜炎的组织平片和切片研究

2015中国遗传学会大会

作者： Hongsong Yu Le Luo Lili Wu Minming Zheng Lijun Zhang Yunjia Liu Hua Li Qingfeng Cao aize kijlstra Peizeng Yang The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute

Previous studies have identified that disturbedapoptosiswas involved in the pathogenesis of Behcet’s disease(BD)and VKH *** study aimsto investigate whether copy number variations(CNVs)of apoptosis-related genes,including FAS,caspase8,caspase3 and BCL-2,are associated with BD and VKH syndrome in Han Chinese.A two-stage association study was performed in 1014 BD patients,1051 VKH syndrome patients and 2076 healthy *** Number Assays and real-time PCR were *** first-stage study showed that increased frequency of high FAS copy number(>2)was found in BD(P=5.42×10)and VKH syndrome(P=2.56×10).Replication and combined study confirmed the association of high copy number(>2)of FAS with BD(P=9.52×10)and VKH syndrome(P=9.77×10).A significant up-regulated mRNA expression of FAS was observed in anti-CD3/CD28 antibodies-stimulated CD4T cells from individuals carrying a high gene copy number(>2)as compared to normal diploid 2 copy number carriers(P=0.004).Moreover,the mRNA expression of FAS both in active patients with BD and VKH syndrome was significantly higher than that in controls(P=0.001 and P=0.007,respectively).In conclusion,our findings suggest that a high copy number of FASgene confers risk for BD and VKH syndrome.

关键词： FAS copy number variation Behcet’s disease VKHsyndrome

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中华眼底病杂志 1996年第1期12卷 33-36页

作者：杨培增 Alex F. de Vos Lidy Broersma aize kijlstra 中山医科大学中山眼科荷兰国家眼科研究所

目的:探讨内毒素诱导的视网膜脉络膜改变和平片、切片结果的差异。方法:从内毒素注射的Lewis鼠制备视网膜和脉络膜-巩膜复合体平片以及眼组织冰冻切片,并进行免疫组织化学染色。结果:平片上显示,注射后4小时单核细胞浸润,随后,大量的单... 详细信息

目的:探讨内毒素诱导的视网膜脉络膜改变和平片、切片结果的差异。方法:从内毒素注射的Lewis鼠制备视网膜和脉络膜-巩膜复合体平片以及眼组织冰冻切片,并进行免疫组织化学染色。结果:平片上显示,注射后4小时单核细胞浸润,随后,大量的单核巨噬细胞浸润至整个视网膜和脉络膜,脉络膜中尚有MHC-Ⅱ类抗原阳性细胞增多;切片上发现,于注射后一定时期,视网膜和脉络膜中有上述细胞浸润。结论:平片技术为视网膜脉络膜原发性严重受累提供了确凿的证据,内毒素诱导的葡萄膜炎可作为人类全葡萄膜炎的动物模型。

关键词：内毒素葡萄膜炎病理学免疫组织化学

实验性自身免疫性葡萄膜视网膜炎中浸润细胞的表型及其凋亡的研究

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中华眼底病杂志 2000年第1期16卷 35-38页

作者：杨培增 Nicole H Herzberg 周红颜黄祥坤谢楚芳金浩丽籍利 Lidy Broersma Mavc D de Smet aize kijlstra 中山医科大学中山眼科中心卫生部眼科学实验室广州510060 The Netherlands Ophthalmic Research Institute Amsterdem Vniversity

目的　探讨实验性自身免疫性葡萄膜视网膜炎 (experimental autoimmune uveoretinitis,EAU)中参与的细胞表型及其凋亡。　方法　用光感受器间维生素 A类结合蛋白 (interphotoreceptorretinoid- binding protein,IRBP)免疫 16只 L ewis鼠... 详细信息

目的　探讨实验性自身免疫性葡萄膜视网膜炎 (experimental autoimmune uveoretinitis,EAU)中参与的细胞表型及其凋亡。　方法　用光感受器间维生素 A类结合蛋白 (interphotoreceptorretinoid- binding protein,IRBP)免疫 16只 L ewis鼠后 ,于眼组织切片和平片上进行免疫组织化学染色和原位凋亡染色 ,所用抗体为抗单核细胞、巨噬细胞 (EDI)、MHC- 类抗原 (OX6 )、T淋巴细胞 (R73)的单克隆抗体 ,所用原位凋亡试剂盒为 TACS1Klenow。　结果　用 IRBP免疫 L ewis鼠后 ,16只鼠中 12只发生了临床可见的葡萄膜炎 ,炎症平均得分为 1.2 9± 0 .7级 ;免疫组织化学染色发现葡萄膜和视网膜中有大量的单核细胞、淋巴细胞及 MHC- +细胞浸润 ,这些组织中均可见浸润细胞的凋亡 ,虹膜睫状体中凋亡细胞明显多于脉络膜和视网膜中的凋亡细胞。　结论　单核巨噬细胞、淋巴细胞和 MHC- +细胞均参与了 EAU的形成 ,在 EAU早期即有浸润细胞发生凋亡 ,此可能是导致这种炎症迅速消退的重要机制。

关键词：葡萄膜炎视网膜炎浸润细胞细胞凋亡 EAU