Vitreous Cavity-Associated Immune Deviation Induced by Retinal S Antigen

Purpose: To determine whether the vitreous cavity(VC) supports the induction of deviant immune responses to retinal soluble(S) antigen and to observe the influence of interleukin-1 (IL-1) on the immunologic properties of the VC. Methods: Retinal S antigen was inoculated into the anterior chamber(AC) and the VC in Wistar rats. Seven days after antigen inoculation, the recipient animals were immunized with S antigen and complete Freund's adjuvant. Delayed-type hypersen- sitivity(DTH) was assessed by footpad challenge. To alter systemic immune conditions,IL-1 was administrated by intraperitoneal injection.Results: Antigen-specific DTH did not develop in rats in which S antigen was injected into the AC and the VC. By contrast, when IL-1 administrated systemically, S antigen was injected into the AC and VC elicited strong DTH.Conclusion: The VC supports immune deviation for soluble antigen by acitivity suppressing antigen-Specific DTH. Systemic administration of exogenous IL-1 eliminates the capacity of the VC to support immune deviation to soluble antigen locally injected.

Practical approach in hepatitis b e antigen-negative individuals to identify treatment candidates

The natural history of chronic hepatitis B is characterized by different phases of infection,and patients may evolve from one phase to another or may revert to a previous phase.The hepatitis B e antigen(HBeAg)-negative form is the predominant infection worldwide,which consists of individuals with a range of viral replication and liver disease severity.Although alanine transaminase(ALT)remains the most accessible test available to clinicians for monitoring the liver disease status,further evaluations are required for some patients to assess if treatment is warranted.Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care.This article aims to assist physicians in the assessment of HBeAgnegative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA,to identify who will remain stable,who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

Prediction, Synthesis and Antigenicity of the Antigenic Peptides of 26kDa Glutathione S-Transferasc of Schistosoma Japonicum (Sj26)

Six antigenic peptides of 26 kDa glutathione S-transferase of Schistosoma japonicum(Sj26) have been predicted according to their hydrophilicity, flexibility. accessibility. chargedistribution and β -turn in the secondary structure by the determination of its primary structure andsynthesized by solid phase method. All of them showed antigenicity with anti-schistosomajaponicum immunoglobulin polyclonal antibody, anti-Sj-lgG PcAb by Dot-ELISA. Three of themshowed good antigenicity. They would serve as candidates of synthetic anti-schistosomal vaccine.

Mapping the Antigenic Peptides of Sm26/2 in Glutathione S-Transferases of Schistosoma Mansoni

Six antigenic peptides of Sm26/2 glutathione S-transferase of schistosoma mansoni have been predicted according to their hydrophilicity, flexibility, accessibility, charge distribution and beta-turn in the secondary structure by the determination of its primary structure, and synthesized by solid phase method. Two of them showed good antigenicity by Dot-ELISA. They would be candidate peptides of synthetic anti-schistosomal vaccine.

A Study of Immunoactivity of Retinal S-Antigen in Retinoblastoma

Purposese:To study retinal S-antigen expression in human retinoblastoma and as-sess if there is a correlation between S-antigen immunoactivity and degree of retinoblastoma cell differentiations.Methods:Ten cases of Chinese retinoblastoma parafin-embedded tissues were ap-plied for this thudy.A strain of monoclonal antibody,MabA9C6,Which defines an epitope in S-antigen retained in fixed-tissue sections,was used to study S-antigen expression in 10 cases of retinoblastomas.S-antigen was localized by the biotina-vidin indirect immunoperoxidase technique and purified MabA9C6 ascites fluid was used with1100dilution.The whole procedure could be finished within a few hours.Results:The S-antigen immunosctivity was observed in different pattterns:the“normal”photorecepto elements incorporated in 3cases of growing tumors;3of 4Fleurettes and E-W rosettes;and scattered tumor cells in50%of the cases.Conclusions:The result suggests that the expression of S-antigen in retinoblas-toma may be used to assess the degree of tumor differentiation as anothe tumor marker in retinoblastoma.

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin's lymphoma

Reactivation of hepatitis B virus(HBV)can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy.Prophylactic administration of lamivudine(LAM)reduces the morbidity and mortality associated with HBV reactivation.However,what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established.HBV reactivation may occur due to the cessation of prophylactic LAM,although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen(HBsAg)seroconversion,which is a satisfactory endpoint for the management of HBV infection.We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma.HBV reactivation developed following cessation of prophylactic LAM therapy.The patient subsequently received treatment with entecavir(ETV),which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion.We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients.A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients.We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy.

前S1抗原检测阴性的HBV感染孕妇血清学和前S1基因特征分析

目的 分析前S1抗原(Pre-S1Ag)检测阴性的HBV感染孕妇血清学特征和前S1基因测序结果,为正确解释HBV感染孕妇中Pre-S1Ag检测无反应性和预防HBV垂直传播提供依据。方法 以2021年7月—2022年12月山东省妇幼保健院健康检查的孕妇为研究对象,检测乙肝五项和Pre-S1Ag,选取乙肝表面抗原(HBsAg)阳性而Pre-S1Ag阴性的标本为实验组共14例,随机选取HBsAg和Pre-S1Ag均阳性的标本为对照组20例,进行HBVDNA定量检测,并扩增PreS/S基因和测序。结果 HBV感染孕妇中Pre-S1Ag阴性仅在HBsAg、抗-HBe、抗-HBc三者均阳性的乙肝五项血清学模式中发现,占比4.17%,其他HBV感染血清学检测模式中未发现;实验组和对照组HBeAg、抗-HBe阳性率均存在显著差异(P <0.001);实验组与对照组比较,HBsAg检测结果分别为(29±91)IU/mL和(2070.6±714.8)IU/mL,HBV DNA定量结果分别为:(1.63±0.05)lgIU/mL和(5.79±1.53) lgIU/mL,差异均有统计学意义(P <0.001);测序结果显示:对照组中有3例B基因型,17例C基因型;实验组14例标本均为C基因型;两组前S1蛋白变异率差异无统计学意义(P>0.05)。结论 HBV感染孕妇中Pre-S1Ag无反应性与PreS基因变异并无相关性,而是与HBV DNA载量低导致Pre-S1Ag表达水平低于检测限有关。不能忽视Pre-S1Ag检测阴性的HBV感染孕妇发生垂直传播的可能性。

昆明地区HBsAg与抗-HBs双阳性慢性HBV感染患者流行病学调查及PreS/S基因突变特征

目的探讨昆明地区HBsAg与抗-HBs(Anti-HBs)双阳性乙型肝炎病毒(HBV)感染患者流行病学及PreS/S基因突变特征。方法选择2018年5月—2022年4月于云南大学附属医院住院及门诊定量检测乙肝两对半的438例慢性HBV感染患者为观察对象,将202例HBsAg(+)/抗-HBs(+)患者作为观察组,将236例HBsAg(+)/抗-HBs(-)患者作为对照组,对比两组患者临床特征。使用巢式聚合酶链反应扩增出PreS/S基因全长序列,确定基因型并分析PreS/S基因突变特征。结果观察组患者在<10岁及高于80岁人群中的流行率较高,而对照组在20~49岁人群中的流行率较高。与对照组比较,观察组患者年龄、HBsAg<250 IU/mL比例、C型HBV感染及乙肝携带者比例均显著增加(P<0.05)。成功扩增PreS/S并测序成功的观察组样本共132例,其中B型基因81例,C型基因51例;对照组样本中B型基因110例,C型基因65例。B型基因患者中,与对照组比较,观察组N末端区域突变率明显增加(P<0.05)。C型基因患者中,与对照组比较,观察组MHR、a决定簇及N末端区域突变率明显增加(P<0.05)。在观察组中,81例B型基因患者中PreS基因缺失突变14例(17.28%),51例C型基因患者中PreS基因缺失突变19例(37.25%),而在对照组中未发现PreS基因缺失突变。结论HBsAg/抗-HBs双阳性HBV感染者在<10岁及高于80岁HBsAg阳性人群多见,HBsAg/抗-HBs双阳性可能与HBsAg突变及PreS基因突变有关。

HBeAg、HBV-DNA、前S_1抗原相关性分析及其临床意义

了解HBeAg、HBV -DNA及前S1抗原相关性及其临床意义。采用ELISA法检测HBV标志物 ,PCR法检测HBV -DNA。 196例不同模式HBV感染者血清HBV -DNA及前S1抗原的总检出率分别为 38 78%和4 0 30 % ,二者无明显差异 (P >0 0 5 )。其中 4 4例HBeAg阳性模式感染者HBV -DNA和前S1抗原的检出率分别为 88 6 4 %和 86 36 % ,两者无明显差异 (P >0 0 5 )。 15 2例不同模式HBeAg阴性感染者HBV -DNA和前S1抗原的检出率分别为 2 4 34%和 2 6 97% ,明显低于HBeAg阳性模式的检出率 ,二者有显著性差异 (P <0 0 5 )。结论 :HBeAg、HBV -DNA及前S1抗原间有着密切的相关性。前S1抗原是病毒复制的又一新标志 ,且与病程的发展及疗效的观察有着重要的意义。

牛S抗原的提取、鉴定及EAU模型的建立

目的 建立实验性自身免疫性葡萄膜炎 (EAU)动物模型 ,研究自身免疫病的发病机制。方法 依据AI—Mahdawi等的方法并加以改进 ,自牛视网膜组织提取S抗原 ,并用其免疫Wistar大鼠。结果 提取的S抗原与文献报告结果大致相同 ,免疫的Wistar大鼠全部出现典型的EAU病变 ,观察临床症状及病理检测。结论 以牛S抗原免疫Wistar大鼠的EAU模型建立成功。

视网膜S抗原在不同动物诱发的实验性自身免疫性葡萄膜视网膜炎

本研究从牛视网膜提纯了S抗原,将其兔疫Hartley豚鼠、SD大鼠和Lewis大鼠,诱发的实验性自身免疫性葡萄膜视网膜炎(EAU)。但其发生率、临床及组织学表现则有很大不同。根据本文的结果及文献报道的结果,作者就其差异的原因及与人类葡萄膜视网膜炎的关联性等方面进行了有关讨论。

非活动性HBsAg携带者临床病理分析

目的了解非活动性HBsAg携带者临床病理特点。方法对80例患者进行生化、病毒标志物及病毒定量检测,并和肝脏病理进行相关性分析。结果光镜下见肝组织基本正常者1例,病理诊断为慢性肝炎轻度者48例,中度以上者19例,占23.75%,活动性肝硬化者12例,占15%;抗HBe阴性组纤维化程度要重于抗HBe阳性组,其中大于S3的抗HBe阴性组患者占总数的60%,阳性组为26%,但肝脏炎症程度与抗HBe水平无关;血小板和胆碱酯酶对于代偿期肝硬化的诊断具有辅助价值。结论对于非活动性HBsAg携带者应尽可能进行肝脏病理检查以明确诊断,并指导治疗。

SE-S抗原的发现及其组织化学与超微结构分布

通过肝脏酶解灌流和密度梯度离心法获得的肝窦内皮细胞作为免疫原，建立一株单克隆抗体ＳＥ－Ｓ，它特异性识别大鼠肝窦内皮细胞，而与其它类型的内皮细胞或非内皮细胞无交叉反应。免疫电镜及免疫印迹分析显示，此抗体所识别的抗原（ＳＥ－Ｓ抗原）位于肝窦内皮细胞的膜表面和胞饮小泡的内表面，分子量为４４～４８ｋＤ。以上结果说明ＳＥ－Ｓ抗原与肝窦内皮细胞的特殊功能密切相关。因此，对于研究不同病理、生理状态下的肝脏。

猪传染性胃肠炎病毒S基因B和C抗原位点片段在毕赤酵母中的表达

采用基因重组的方法构建了含有猪传染性胃肠炎病毒S基因B和C抗原位点片段的巴斯德毕赤酵母Pichiapastoris分泌型表达载体pPIC9K-ts,经线性化后采用电穿孔法将其导入毕赤酵母GS115中,大量筛选后获得高效表达外源蛋白的毕赤酵母工程菌株GS115/pPIC9K-ts。表达蛋白经Dot-ELISA检测具有良好的抗原性。本研究为TGE的血清学检测方法的建立提供了必要的物质基础。

细粒棘球蚴GST抗原表位的生物信息学预测

目的应用生物信息软件分析细粒棘球蚴谷胱甘肽S-转移酶(EgGST)的蛋白二级结构并预测B淋巴细胞表位和T淋巴细胞表位,为后续表位疫苗的设计研究提供基本的数据和资料。方法采用DNAstar软件、ProPred MHC Class-ⅡBinding Peptide Prediction Server和Biosun软件对EgGST的B淋巴细胞表位和T淋巴细胞表位进行预测。结果预测EgGST存在8个B淋巴细胞表位区域和7个T淋巴细胞表位。结论分析预测的EgGST抗原表位将对后续的表位疫苗研究具有重要意义。

哺乳动物细胞分泌的乙型肝炎病毒表面S+PreS1融合抗原的理化和生物学性状

研究了哺乳动物细胞(转基因GdSS1-18细胞系)分泌的乙型肝炎(乙肝)病毒表面S+PreS1融合抗原(SS1)纯品的理化及生物学性状,结果表明:经HPLC柱层析呈现一个对称峰,证明HBsAg颗粒所带电荷的均一性;SDS-PAGE出现P24及P27条带,未出现Gp30的条带,凝胶扫描分析其各条带分别各占22 3%、77 7%、0%;West ernblot试验证实,P27和Gp30能与S及S1抗体结合,而P24条带仅能与S抗体结合,表明S、PreS1是特异性条带;N-末端的氨基酸序列与所用目的基因编码的序列相同;乙肝SS1融合抗原在4℃储存较稳定。动物实验结果表明:与单纯含S基因的参比疫苗相比,含SS1融合基因疫苗免疫Balb/c小鼠既产生S抗体,又产生S1抗体,S抗体的ED50滴度与参比疫苗相似,S1抗体产生早于S抗体。

伤寒沙门氏菌SOD的提取及抗原性研究

经硫酸铵分级沉淀，ＤＥＡＥ纤维素柱层析提取了伤寒沙门氏菌ＳＯＤ。提取后酶的比活性为３２７０Ｕ／ｍｇ，经聚丙烯酰胺凝胶电泳，蛋白质染色及酶活性染色显示提取的ＳＯＤ达到了电泳纯。酶活性染色法和原子吸收分光光度法测定结果表明提取的ＳＯＤ为Ｆｅ－ＳＯＤ。双向琼脂扩散试验结果显示抗伤寒沙门氏菌Ｆｅ－ＳＯＤ血清与牛红细胞ＳＯＤ不形成沉淀线，提示伤寒沙门氏菌Ｆｅ－ＳＯＤ与牛红细胞ＳＯＤ无交叉反应，抗体对酶活性抑制试验结果显示抗Ｆｅ－ＳＯＤ血清可抑制伤寒沙门氏菌及鼠伤寒沙门氏菌的Ｆｅ－ＳＯＤ和Ｆｅ／Ｍｎ－ＳＯＤ活性，对Ｍｎ－ＳＯＤ活性无抑制作用，说明伤寒沙门氏菌和鼠伤寒沙门氏菌的ＳＯＤ之间有共同抗原，也提示ＳＯＤ的辅基似乎决定了其抗原特异性。

猪传染性胃肠炎病毒S基因抗原位点B与C之间片段的克隆与原核表达

将RT-PCR扩增的猪传染性胃肠炎病毒S基因抗原位点B与C之间的目的片段经克隆、双酶切后连接于表达载体,经酶切、PCR和测序鉴定的阳性重组质粒转化BL21(DE3),用IPTG诱导重组菌株表达其融合蛋白。结果显示,目的片段的大小为357bp,序列分析表明,S基因与其他猪传染性胃肠炎病毒相应基因具有很高的同源性;Western-blotting检测表明,分子质量约34ku的融合蛋白具有良好的反应原性。

乙肝表面抗原小蛋白S基因导入番茄的遗传转化体系的建立

以丽春番茄无菌苗的子叶为外植体,以农杆菌菌株EHA105(包含质粒pBin438S)为载体,将乙肝表面抗原小蛋白S基因导入番茄组织中.基本培养基采用MS+6-BA1 0mg/L+IAA0 2mg/L,在共培养时加入乙酰香酮100μmol/L作为诱导剂,经过组织培养得到转基因植株.对转化植株基因组进行的分子学PCR检测表明,外源基因有可能已整合到番茄基因组中.该转基因遗传体系的建立为利用转基因植物生产乙肝口服疫苗奠定了基础.