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.     

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。     

Induction of Donor-Specific Allograft Tolerance by Short-Term Treatment with LF15-0195 After Transplantation. Evidence for a Direct Effect on T-Cell Differentiation

A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms.     

抗蝮蛇毒磷酸二酯酶单克隆抗体的制备及鉴定

从蝮蛇毒中提取磷酸二酯酶,用此酶免疫BALB/c小鼠,取其脾细胞与小鼠骨髓瘤细胞Fo融合,以间接ELISA检测杂交瘤细胞培养上清液和小鼠腹水中的特异性抗体,其效价分别为1∶128和1∶51 200.抗原阻断试验结果表明,此抗体对蛇毒磷酸二酯酶具有特异性.该杂交瘤细胞株定为G_8,该株单抗属鼠IgG_(2a)亚型,经体外持续培养6个月,其分泌抗体性能稳定.     

丁型肝炎病毒中国SZ株的cDNA克隆及基因变异分析

以四川地区１例无症状携带丁型肝炎病毒（ＨＤＶ）和乙型肝炎病毒（ＨＢＶ）患者的外周血为标本，采用逆转录－ＰＣＲ技术，获得了ＨＤＶ全基因组的ｃＤＮＡ克隆（ＨＤＶＳＺ９３株），全长１６８４ｂｐ。与世界其他七个地区株相比，其核酸同源性为８１．８％～９５．４％；丁肝病毒抗原蛋白编码区核酸同源性为８８．９％～９６．１％，氨基酸同源性为８６，４％～９３．０％。另从１例慢性重型肝炎患者血清内克隆了丁肝病毒抗原蛋白（ＨＤＡｇ）编码基因（ＨＤＶ－ＳＺ９２株），与ＳＺ９３株相比，亦存在若干变异。对这些不同地区、不同病情ＨＤＶ株变异的可能意义进行了讨论。     

128对不育夫妇血清、精浆抗精浆免疫抑制物抗体与精液检查关系的分析

我们检测了８９对生育夫妇和１２８对不育夫妇血清、精浆中抗精浆免疫抑制物抗体（ＳＰＩ—Ａｂ）的水平。结果表明，不育夫妇血清、精浆ＳＰＩＭ—Ａｂ的水平和检出率均明显高于生育组（Ｐ＜０．０１）；精浆ＳＰＩＭ—Ａｂ水平增高者的精子密度、精子活率、精子运动速度和ＳＰＩＭ活性均明显降低（Ｐ＜０．０１）。提示：ＳＰＩＭ—Ａｂ水平增加可能影响生育。     

Enhancement of in vivo and in vitro immune functions by a conformationally biased,response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design

A conformationally biased, agonist of human C5a_65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88^−/−). Serum from mice immunized with EP67–ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88^−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.     

抗中性粒细胞胞浆抗体在肾小球疾病中的检测及临床意义

目的:检测各种肾小球疾病患者血清中抗中性粒细胞胞浆抗体(ANCA)并探讨其临床意义。方法:应用间接免疫荧光法(IIF)检测20例正常人及131例各种肾小球疾病患者血清中ANCA。结果:131例患者中有11例ANCA阳性性(阳性率为8.4％),且均为P-ANCA阳性,而20例正常对照组无1例阳性(P<0.05)。ANCA阳性中以新月体性肾炎、狼疮性肾炎、紫癜性肾炎的阳性率较高,分别为67％、25％、16.7％。新月体性肾炎与IgA肾病等原发性肾小球疾病组比较有显著性差异(P<0.05)。结论:ANCA在各种肾小球疾病中并不少见,尤其是新月体性肾炎、狼疮性肾炎、紫癜性肾炎的阳性率较高,推测ANCA可能在这些疾病的发病机理中起了一定的作用。     

安徽省1991～1995年脊髓灰质炎实验室监测结果分析

安徽省１９９１～１９９５年共报告ＡＦＰ８０３例，其中采集粪便标本５１２例，占６３．７６％，从中分离出脊灰病毒３７株，其它肠道病毒８６株，共１２３株，阳性率为２４．０２％，以上脊灰病毒除１９９１年６株未作型内鉴别外，其余经型内鉴别，均确定为疫苗相关株。１９９４年和１９９５年的脊灰病毒带毒率调查中，共采集１５３３份粪便标本，分离出脊灰病毒１８株，其它肠道病毒１３８株，１９９４年分离的１４株脊灰病毒经型内鉴别，亦确定为疫苗相关株。１９９３年０～３岁儿童脊灰中和抗体测定，三个型别抗体阳性率均在９６％以上，处于较高水平。自１９９２年以来，已连续４年未发现脊灰野病毒的存在，说明本省已基本阻断了脊灰野病毒的传播。