Immunization with BLS-Stx2B chimera totally protects dams from early pregnancy loss induced by Shiga toxin type 2 (Stx2) and confers anti-Stx2 immunity to the offspring

Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved in food-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC and is responsible for systemic complications including Hemolytic Uremic Syndrome (HUS). It has been previously demonstrated that Shiga toxin type 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. The main purpose of this study was to determine if an active immunization prevents Stx2 mediated pregnancy loss and confers passive protective immunity to the offspring. For that purpose Sprague Dawley female rats were immunized with the chimera based on the enzyme lumazine synthase from Brucella spp. (BLS) and the B subunit of Shiga toxin 2 (Stx2B) named BLS-Stx2B. After immunization females were mated with males. At day 8 of gestation, dams were challenged intraperitoneally with a sublethal and abortifacient dose of Stx2. The immunization induced high anti-Stx2B-specific antibody titers in sera and most important, prevented pregnancy loss. Pups born and breastfeed by immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fostering experiments indicated that passive protective immunity against Stx2 was transmitted through lactation. These results indicate that immunization of adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss and confers anti Stx2 protective immunity to the offspring.     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

Sensitization Following LVAD Implantation Using Leucodepleted Blood Is Not Due to HLA Antibodies

Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.     

bevacizumab治疗乳腺癌的基础和临床研究

分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

达利珠单抗预防致敏受者肾移植后排斥反应的临床研究

目的　探讨用达利珠单抗诱导治疗预防致敏受者肾移植后急性排斥反应的有效性与安全性。方法　将 36例群体反应性抗体为 30 %～ 5 0 %的致敏受者随机分为舒莱组和对照组 ,各 18例 ,舒莱组患者于移植术前 2h和术后第 4d接受达利珠单抗 (2 0mg/次 )诱导治疗 ,两个组术后均以环孢素A、霉酚酸酯和皮质激素预防排斥反应。结果　舒莱组术后 3个月内的急性排斥反应发生率明显低于对照组 (P <0 .0 1) ;术后 2～ 4周内对照组平均每日皮质激素用量明显高于舒莱组 ;两个组人 /肾 1年存活率的差异无显著性 ;舒莱组术后肾功能的恢复较对照组快 ,但差异无显著性 ;舒莱组术后1周内CD2 5 淋巴细胞数明显降低 (P <0 .0 1) ;未观察到达利珠单抗的相关不良反应。结论　在合理筛选供受者的基础上 ,致敏受者肾移植前接受达利珠单抗诱导治疗可降低术后急性排斥反应的发生率 ,且较为安全。     

99Tcm标记人源化抗人血小板膜糖蛋白Ⅲ a单克隆抗体SZ21F(ab)2血栓栓塞显像

目的用动物血栓栓塞模型显像评估99^Tc^m标记人源化抗人血小板膜糖蛋白（GP）Ⅲa单克隆抗体（简称单抗）F（ab）2片段SZ21F（ab）2的应用价值。方法通过体外抑制二磷酸腺苷（ADP）诱导的犬血小板聚集实验，评估SZ21F（ab）2与血小板结合的亲和性和特异性。以2-亚氨基噻吩盐酸盐（IT）法修饰SZ21F（ab）2分子的亚氨基，以99^Tc^m-葡庚糖酸钠（GH）转换络合法进行标记。分别用快速薄层层析（ITLC）法和ELISA测定标记物的放化纯及生物活性。对3条肺动脉血栓和8条（包括上述3条）后肢深静脉血栓栓塞比格犬模型进行显像研究。结果SZ21F（ab）2抑制ADP诱导的犬富含血小板血浆（PRP）聚集实验的半数有效剂量（IC50）为（2．49±1．88）μg／ml。ITLC法测得标记物的放化纯为90％～95％，ELISA测定结果表明标记后抗体保留了免疫活性。注射显像剂后1h，肺动脉血栓部位和后肢深静脉血栓部位均出现放射性浓聚。注射后3h，在体显像肺动脉血栓和后肢深静脉血栓栓塞模型的放射性靶／本底（T／B）比值分别为3．03±1．18和3．51±0.62。肺动脉血栓部位和后肢深静脉血栓部位的每克组织百分注射剂量率（％ID／g）分别为0．083％ID／g和0．076％ID／g。体外检测结果表明：肺动脉血栓与正常肺组织的单位质量放射性比值平均为12．8，后肢深静脉血栓与血液的单位质量放射性比值平均为5．2，与肌肉的比值平均为127.0。结论99^Tc^m-SZ21F（ab）2与人血小板具有较高的亲和力，有潜在的血栓显像应用前景。     

40例形态学和免疫学分型不一致的急性白血病分析

选用一组国产敏感特异的McAb,采用APAAP桥联免疫酶标组化染色技术对40例形态学和免疫学分型不一致的急性白血病进行了分析。结果表明,32例形态学难以分类或虽能分类但与免疫学分型不同的急性白血病均有明确的细胞系列特异性标记表达。其中B-ALL14例、T-ALL1例、ANLL2例、同时表达T和B系相关分化抗原的双标-ALL 11例、HAL4例,同时表达淋巴和髓系相关的特异性标记。有8例未测到任何标记抗原,归属于急性未分化型白血病。     

保定地区首次证实为流行性出血热疫源地

保定地区1934年首次经血清学证实有EHF病例发生,并从疫区鼠类中查到EHF抗原,其阳性率分别为:褐家鼠4.85%,黑线姬鼠1.95%,大仓鼠0.79%,小家鼠0.51%,褐家鼠可能是我区的主要传染源。疫区健康人群血清EHF抗体阳性率为1.37%,女性显著高于男性。     

抗人精浆蛋白McAb的制备及其特性研究

本文报道用杂交瘤技术建立了２株分泌抗人精浆蛋白单克隆抗体的细胞株Ｄ１和Ｃ１２。Ｄ１株分泌的抗体为ＩｇＭ，Ｃ１２株为ＩｇＧ３。这两株均能与正常人精浆和无精子症患者的精浆产生特异性免疫反应。Ｄ１株单抗具有补体依赖性制动人精子的作用，间接免疫荧光试验表明，它能结合到人精子颈部和顶体后区。这充分说明２株单抗是特异性抗人精浆的，Ｄ１是精子制动抗体，其相应的精子抗原属于精子外套抗原成分之一。