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ifn-α抗病毒治疗118例慢性乙型肝炎并10年随访分析

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南昌大学学报（医学版） 2024年第3期64卷 6-10,37页

作者：龙林吴志国周瑶向海鸿邱芳罗小露刘翠芸孙水林南昌大学第二附属医院感染科南昌330006 重庆建设医院医务科重庆400050

目的探讨ifn-α抗病毒治疗慢性乙型肝炎(CHB)患者的效果,为CHB的抗病毒治疗提供参考。方法选取接受普通ifn-α治疗且资料完整的CHB患者118例,通过门诊定期复诊和电话随诊收集患者的乙肝五项[乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体... 详细信息

目的探讨ifn-α抗病毒治疗慢性乙型肝炎(CHB)患者的效果,为CHB的抗病毒治疗提供参考。方法选取接受普通ifn-α治疗且资料完整的CHB患者118例,通过门诊定期复诊和电话随诊收集患者的乙肝五项[乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体(HBsAb)、乙型肝炎e抗原(HBeAg)、乙型肝炎e抗体(HBeAb)、乙型肝炎核心抗体(HBcAb)]、乙肝DNA定量(HBV-DNA)和谷丙转氨酶(ALT)水平。比较治疗前后、随访期间不同时间点的HBV-DNA和HBsAg阴转率、HBeAg/HBeAb血清转换率和ALT复常率等。结果 HBV-DNA阴转率及HBsAg阴转率随治疗时间的延长而提高,HBV-DNA阴转率在治疗第24、36、48周时的阴转率明显高于第12周,HBsAg阴转率在治疗第48周明显高于第12周和24周,差异均有统计学意义(P0.05)。病毒学复发率停药后先上升,在停药第144周呈现稳定趋势。ALT复常率在停药第144周呈现稳定趋势,停药第144周的ALT复常率明显高于停药第12周(Pifn-α抗病毒治疗CHB可取得较好的疗效,在治疗及停药后各随访节点,HBV-DNA阴转率、HBsAg阴转率、ALT复常率、HBeAg/HBeAb转换率均可获得较高的应答率。

关键词：慢性乙型肝炎抗病毒治疗 ifn-α 疗效

ifn-αIL-6和IL-17检测对结核病辅助诊断价值

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河北医学 2024年第6期30卷 942-945页

作者：刘战地孙明玥田二朋马伟立邸红芹河北省胸科医院河北石家庄050033

目的:评价血清免疫细胞因子对结核分枝杆菌肺病(TB)的诊断价值。方法:回顾性选取2020年11月至2022年10月于河北省胸科医院就诊的139例疑似肺结核患者作为研究对象。按照2018年最新实施的肺结核诊断标准(WS288-2017),其中确诊结核病69例... 详细信息

目的:评价血清免疫细胞因子对结核分枝杆菌肺病(TB)的诊断价值。方法:回顾性选取2020年11月至2022年10月于河北省胸科医院就诊的139例疑似肺结核患者作为研究对象。按照2018年最新实施的肺结核诊断标准(WS288-2017),其中确诊结核病69例,纳入结核组,非结核病70例纳入非结核组。采用流式免疫荧光发光法检测血清中免疫相关细胞因子IL-6、IL-17和ifn-α水平,并分析三种因子检测对结核病的诊断效能。结果:结核组患者IL-6浓度和IL-17浓度显著高于非结核组,差异有统计学意义(Pifn-α浓度略高于非结核组,但差异无统计学意义(P>0.05);进行ROC曲线分析:IL-6检测AUC面积为0.658(Pifn-α检测AUC面积为0.571(P<0.001)。结论:MTB感染者IL-6、IL-17水平增高,IL-6、IL-17对结核的诊断具有较好的灵敏度和特异度;IL-6、IL-17在临床辅助诊断结核病具有一定的价值。

关键词：结核病细胞因子 ifn-α IL-6 IL-17

The Effect of Bovine ifn-α on the Immune Response in Guinea Pigs Vaccinated with DNA Vaccine of Foot-and-Mouth Disease Virus

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 701-706页

作者： Hui-Chen GUO, Zai-Xin LIU*, Shi-Qi SUN, Qing-Wen LENG1, Dong LI, Xiang-Tao LIU, and Qing-Ge XIE* Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China College of Animal Science and Technology, Shihezi University, Shihezi 832003, China 1 Key Laboratory of Animal Virology of Ministry of Agriculture Lanzhou Veterinary Research Institute Chinese Academy of Agricultural SciencesLanzhou 730046 China College of Animal Science and Technology Shihezi UniversityShihezi 832003 China

In this study, we constructed recombinant plasmid pcDNA3.1/P12X3C3D including P1, 2A, 3C, 3D and part of 2B gene of FMDV and pcDNA3.1/ifn containing the gene encoding bovine ifn-α. We inoculated the DNA vaccine pcDNA3.1/P12X3C3D with or without pcDNA3.1/ifn to evaluate the effi- ciency of this DNA vaccine and the immunogenicity of DNA vaccine enhanced by the co-delivery with pcDNA3.1/ifn. After two times of vaccination with DNA vaccine, all of guinea pigs were challenged with 103 ID50 FMDV type O. Anti-FMDV antibody levels were detected by ELISA and T lymphocyte proliferation response was tested by MTT assay. The result shows that guinea pigs inoculated by pcDNA3.1/P12X3C3D alone or with pcDNA3.1/ifn generated specific antibodies and induced an FMDV-specific T lymphocyte proliferation response. FMDV challenge tests showed that one in four guinea pigs immunized by pcDNA3.1/ P12X3C3D with pcDNA3.1/ifn was protected from the FMDV serotype O infection. This result indicated that the efficiency of the DNA vaccine was enhanced by co-delivery with pcDNA3.1/ifn. However, the protection rate was considerably lower than that immunized with conventional FMD vaccine.

关键词： foot-and-mouth disease virus (FMDV) DNA vaccine ifn-α gene vaccination

High ifn-α expression is associated with the induction of experimental autoimmune uveitis (EAU) in Fischer 344 rat

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Cell Research 2001年第4期11卷 293-300页

作者： HU YONG JUN, LEI ZANG, YA DI WU, BING SUN Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Laboratory of Molecular Immunology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-a are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA + R16 + PTX treated (CRP- treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, ifn- mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and ifn-a mRNA expression were compared in the experimental groups, only ifn-a mRNA expression was associated with EAU development. To distinguish the sources of ifn-a producing cells, it was observed that ifn-a expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant ifn-a in the presence of PTX. The data strongly suggested that ifn-a might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High ifn-a expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat.

关键词： Experimental autoimmune uveitis(EAU) fischer 344 rat ifn-α pertussis toxin(PTX).

Ligation of CD180 inhibits ifn-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

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Cellular & Molecular Immunology 2017年第2期14卷 192-202页

作者： Ming You Guanjun Dong Fanlin Li Feiya Ma Jing Ren Yujun Xu Huimin Yue Ruijing Tang Deshan Ren Yayi Hou The State Key Laboratory of Pharmaceutical Biotechnology Division of Immunology Medical School Nanjing University Nanjing 210093 People's Republic of China Jiangsu Key Laboratory of Molecular Medicine Medical School Nanjing University Nanjing 210093 People's Republic of China oth Ming You and Guanjun Dong contributed equally to this work

A hallmark of systemic lupus erythematosus （SLE） is the consistent production of various auto-antibodies by auto-reactive B cells. Interferon-α（ifn-α） signaling is highly activated in SLE B cells and plays a vital role in the antibody response by B cells. Previous studies have shown that CD180-negative B cells, which are dramatically increased in SLE patients, are responsible for the production of auto-antibodies. However, the association between CD180 and ifn-αsignaling remains unknown. In the present study, we explored the effect of CD180 on regulating the activation of ifn-α signaling in B cells. We found that the number of CD180-negative B cells was increased in MRIJMp-Fas（Ipr/Ipr） lupus-prone mice compared with wild-type mice. Phenotypic analysis showed that CD180-negative B cells comprised CD138＋ plasmablast/plasma cells and GL-7＋ germinal center （GC） B cells. Notably, ligation of CD180 significantly inhibited the I FN-α-induced phosphorylation of signal transducer and activator of transcription 2 （STAT-2） and expression of ifn-stimulated genes （ISGs） in a Lyn-PI3K-BTK-dependent manner in vitro. Moreover, ligation of CD180 could also inhibit ifn-α-induced ISG expression in B cells in vivo. Furthermore, the Toll-like receptor 7 and Toll-like receptor 9 signaling pathways could significantly downregulate CD180 expression and modulate the inhibitory effect of CD180 signaling on the activation of I FN-a signaling. Collectively, our results highlight the close association between the increased proportion of CD180-negative B cells and the activation of ifn-α signaling in SLE. Our data provide molecular insight into the mechanism of ifn-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment.

关键词： B cells CD180 ifn-α SLE

Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of ifn-α

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Cellular & Molecular Immunology 2020年第5期17卷 519-532页

作者： Min Wu Liuchuang Gao Miao He Hangyu Liu Han Jiang Ketai Shi Runshi Shang Bing Liu Shan Gao Hebin Chen Feili Gong Erwin WGelfand Yafei Huang Junyan Han Department of Immunology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Respiratory Medicine Zhongnan Hospital of Wuhan UniversityWuhanChina Department of Respiratory Diseases Wuhan Central HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Pulmonary Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Division of Cell Biology Department of PediatricsNational Jewish HealthDenverCOUSA Department of Pathogen Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early *** responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain *** dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal *** report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma *** transfer of pDCs or administration of ifn-αto neonatal mice prevented the development of allergic inflammation in wild type but not in ifnAR1−/−***,adult mice developed more severe allergic inflammation when pDCs were *** protective effects of pDCs were mediated by the pDC-/ifn-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the *** asthmatic patients,the percentage of pDCs and the level of ifn-αwere lower in children than in *** results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.

关键词： Neonate Plasmacytoid Dendritic Cells Allergic airway inflammation ifn-α Airway epithelial cells

金黄色葡萄球菌对BV2细胞ifn-α生成的影响

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畜牧兽医学报 2022年第8期53卷 2633-2641页

作者：卢婉青赵莎莎蒋松宏童智子黄丹妮郭建华吴俊伟周洋西南大学动物医学院重庆402460 西南大学医学研究院免疫学研究中心重庆402460

旨在探究金黄色葡萄球菌(Staphylococcus aureus,简称金葡菌)对小胶质细胞α干扰素(interferonα,ifn-α)生成的影响,本研究先用金葡菌感染BV2细胞,检测ifn-α的mRNA表达、分泌到细胞培养液上清的量以及TBK1/IRF3通路的激活情况,再分别... 详细信息

旨在探究金黄色葡萄球菌(Staphylococcus aureus,简称金葡菌)对小胶质细胞α干扰素(interferonα,ifn-α)生成的影响,本研究先用金葡菌感染BV2细胞,检测ifn-α的mRNA表达、分泌到细胞培养液上清的量以及TBK1/IRF3通路的激活情况,再分别用TBK1抑制剂BX-795和amlexanox、NF-κB抑制剂IMD-0354处理细胞,检测TBK1/IRF3的激活以及ifn-α水平。结果表明,BV2感染金葡菌后,ifn-α转录水平在3~12h升高,6~12h释放量增加,呈剂量依赖性,TBK1和IRF3的转录水平和蛋白水平未发生变化,但在1~12h其磷酸化水平升高,表明金葡菌激活BV2细胞TBK1/IRF3通路,BX-795、amlexanox和IMD-0354处理细胞后,IRF3磷酸化水平降低,ifn-α生成减少,表明TBK1和NF-κB参与金葡菌促进BV2细胞生成ifn-α。综上所述,金葡菌感染BV2后促进ifn-α生成,且该过程依赖于TBK1和NF-κB,本结果为临床防治中枢神经系统感染金葡菌提供了可能靶点和理论基础。

关键词：金黄色葡萄球菌 BV2 ifn-α TBK1 IRF3

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HBV通过下调PTEN的表达拮抗ifn-α抗病毒活性

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安徽医科大学学报 2022年第6期57卷 953-957页

作者：樊星语胡冰琪黄俊峰杨英刘欢欢张浩王琴周强陈礼文安徽医科大学第二附属医院检验科合肥230601

目的探讨乙型肝炎病毒(HBV)感染所致的第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)下调与α-干扰素(ifn-α)抗病毒活性的相关机制。方法在适宜条件下培养HepG2细胞和HepG2.2.15细胞,以空白载体(pcDNA3.1)和HBV1.3质粒分别转... 详细信息

目的探讨乙型肝炎病毒(HBV)感染所致的第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)下调与α-干扰素(ifn-α)抗病毒活性的相关机制。方法在适宜条件下培养HepG2细胞和HepG2.2.15细胞,以空白载体(pcDNA3.1)和HBV1.3质粒分别转染HepG2细胞,Western blot法检测PTEN蛋白质的表达;将pcDNA3.1和PTEN过表达(PTEN-OE)质粒分别瞬时转染HepG2.2.15细胞,化学发光法分析细胞培养上清液中HBV相关抗原的表达,实时荧光定量PCR(qRT-PCR)技术分析HBV前基因组RNA(HBV pgRNA)表达;使用合成RNA双链体poly(I∶C)刺激PTEN-OE的细胞,qRT-PCR技术分析ifn-αmRNA的表达,Western blot法分析JAK/STAT信号通路中干扰素调节因子9(IRF9)、黏病毒抗性蛋白1(MxA)的表达。结果瞬时表达HBV的HepG2细胞和稳定表达HBV的HepG2.2.15细胞中,PTEN蛋白的表达降低;PTEN-OE的HepG2.2.15细胞中,HBV相关抗原及HBV pgRNA的表达较对照组降低,经poly(I∶C)作用后,ifn-αmRNA水平较对照组显著升高,且JAK/STAT信号通路相关蛋白IRF9、MxA的表达增加。结论 HBV可能通过下调PTEN的表达发挥拮抗ifn-α抗病毒活性的作用。

关键词：乙型肝炎病毒 PTEN ifn-α JAK/STAT信号通路慢性乙型病毒性肝炎

外周血CD39+Treg细胞及TNF-α、ifn-α的表达在斑秃发病中的研究

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外周血CD39+Treg细胞及TNF-α、IFN-α的表达在斑秃发病中的研究

作者：程晓曼郑州大学

学位级别：硕士

研究背景与目的斑秃(alopecia areata,AA)是皮肤科门诊常见的以毛囊为靶器官的慢性炎症性疾病,一般无自觉症状且患处皮肤正常。斑秃不仅影响一个人的外貌,往往也给患者的心理带来很大的负面影响。目前普遍认为AA是在一定的遗传背景基础... 详细信息

研究背景与目的斑秃(alopecia areata,AA)是皮肤科门诊常见的以毛囊为靶器官的慢性炎症性疾病,一般无自觉症状且患处皮肤正常。斑秃不仅影响一个人的外貌,往往也给患者的心理带来很大的负面影响。目前普遍认为AA是在一定的遗传背景基础上,外界环境的诱发下引起的一种由T淋巴细胞介导的自身免疫性疾病,涉及毛囊免疫豁免权的崩溃、细胞毒性免疫细胞识别毛囊相关自身抗原并产生免疫应答等多种因素,多种细胞及细胞因子均可能在AA的发生发展中起重要作用。其中,Treg细胞(调节性T细胞)是CD4+T细胞亚群之一,在调节自身耐受性、肿瘤免疫、抗微生物耐药性、过敏和移植排斥等方面发挥重要作用,研究发现Treg细胞可能参与AA的发病,且CD39+Treg细胞比CD39-Treg细胞作用更强。尽管近年来Treg细胞是研究热点,但AA患者外周血中CD39+Treg细胞的绝对值水平鲜有报道,因此,本文检测了 AA患者外周血中CD39+Treg细胞的绝对值,旨在对AA免疫相关机制进行探讨和补充。肿瘤坏死因子-α(TNF-α)是一种Th1型促炎性细胞因子,与多种自身免疫性疾病如银屑病、系统性红斑狼疮(SLE)等有着密切的联系。先前有研究表明某些TNF-α基因多态性与AA相关。事实上,其在AA中的确切功能尚不十分明确,并且仍然存在争议。TNF-α可能参与AA的发生,但阻断TNF-α亦可能诱发或加重AA。干扰素-α(ifn-α)是另一种主要由浆细胞样树突状细胞(PDCs)分泌的Th1型细胞因子,目前已有多项研究证实ifn在炎症性疾病如SLE、扁平苔藓等中的作用。而在ifn-α-2b和利巴韦林治疗丙肝病毒感染期间继发AA或普秃(AU)的病例则提示了ifn-α在AA发生中的作用。TNF-α和ifn-α广泛参与各种自身免疫性疾病的发病机制,并具有相互关系。AA患者血清TNF-α和ifn-α水平之间的相关性及其与AA严重程度、疾病活动性和病程长短的关系尚未得到充分研究。本研究的目的是检测AA患者的血清TNF-α和ifn-α水平,阐明这两种细胞因子之间是否存在平行或相互关系,并评估两种细胞因子水平与疾病严重程度、疾病活动性和病程长短之间的关系。资料与方法纳入符合Oslen斑秃指南诊断标准的20例AA患者,并排除其它病因引起的脱发以及合并其他自身免疫性疾病者。将纳入的20例AA患者分为轻型AA组与重型AA组、活动期AA组与稳定期AA组、≦6个月组与>6个月AA组,分别应用流式细胞术和酶联免疫吸附法(ELISA)检测外周血中CD39+Treg细胞的绝对值及血清TNF-α、ifn-α的水平,并与20例健康志愿者进行比较。对实验所得的数据采用SPSS21.0软件进行统计学处理。正态分布的计量资料以均数±标准差(X±S)表示,两独立样本均数间的比较行t检验(方差不齐时行t’检验),不满足正态的以中位数(25%分位数,75%分位数)[M(P25-P75)]表示,用曼-惠特尼秩和检验,p6月组和≦6月组AA患者CD39+Treg细胞绝对值均高于对照组,差异有统计学意义(p6月组和≦6月组之间外周血CD39+Treg细胞绝对值差异无统计学意义(p>0.05)。2 血清TNF-α水平及ifn-α水平AA组患者血清TNF-α水平高于对照组,差异无统计学意义。轻型AA组和重型AA组、活动期组和稳定期组、病程>6月组和≦6月组AA患者及其与对照组之间血清TNF-α水平差异均无统计学意义(p>0.05)。AA组患者血清ifn-α水平高于对照组,且重型AA组显著高于对照组及轻型AA组,活动期组、病程≦6月组均高于对照组,差异有统计学意义(p6月组与病程≦6月组之间、病程>6月组与对照组之间血清ifn-α水平差异无统计学意义(p>0.05)。3 相关性分析AA患者血清TNF-α与ifn-α水平呈正相关(r=0.621,p=0.003),AA患者外周血CD39+Treg细胞绝对值与血清TNF-α(r=-0.178,p=0.454)、ifn-α(r=0.26,p=0.268)水平之间未见明显相关性。结论1.斑秃患者外周血CD39+Treg细胞的绝对值及血清TNF-α、ifn-α水平均异常升高,三者均可能参与了斑秃的免疫调节过程。2.斑秃患者血清TNF-α与ifn-α水平呈正相关,表明二者

关键词：斑秃 CD39+Treg细胞 TNF-α ifn-α