IMMUNITY IN HUMAN SCHISTOSOMIASIS-MANSONI - REGULATION OF PROTECTIVE IMMUNE-MECHANISMS BY IGM BLOCKING ANTIBODIES
IMMUNITY IN HUMAN SCHISTOSOMIASIS-MANSONI - REGULATION OF PROTECTIVE IMMUNE-MECHANISMS BY IGM BLOCKING ANTIBODIES
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DOI：
10.1084/jem.164.5.1626
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发表时间：
1986-11-01
影响因子：
15.3
通讯作者：
OUMA, JH
中科院分区：
文献类型：
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作者：
KHALIFE, J;CAPRON, M;OUMA, JH
在大鼠实验性血吸虫病中证实了封闭抗体后，在人血吸虫病中调查了这些因素的存在。在曼氏血吸虫感染患者血清中，通过蛋白A-琼脂糖凝胶（PAS）吸收或快速蛋白液相色谱（FPLC）去除给定同种型（IgM）可诱导IgG介导的对S.嗜酸性粒细胞对曼氏童虫的影响。抑制实验表明，富含IgM的组分（PAS流出物）能够抑制由IgG组分（总血清或PAS洗脱液）介导的嗜酸性粒细胞依赖性细胞毒性。感染人血清中的IgG和IgM抗体均能免疫沉淀标记的精子表面去污剂提取物中的30，000 - 40，000 Mr抗原。通过使用两种针对38，000 Mr抗原的放射性标记mAb（IPLSm 1、IPLSm 3）进行竞争实验，表明IgG和IgM对该抗原具有特异性。此外，可以直接证明针对Mr 38，000抗原的IgG和IgM抗体之间的交叉免疫。在体内的相关性，这样的IgM封闭抗体在人类免疫血吸虫病的背景下进行了评估，在两组儿童分类为耐药或易感治疗后再感染。通过捕获试验测量特异性针对38，000 Mr抗原的IgM抗体。IgM抗体的平均水平显着高于敏感组在耐药组治疗前后。这些结果是一致的想法，血吸虫病的免疫力不仅可以归因于具有确定的效应功能的抗体的存在，但也没有封闭抗体。在人类血吸虫病中存在的抗体同种型阻断效应器对确定的表面靶点的反应的描述可能会导致一个新的理解的机制调节免疫再感染对寄生虫和可能的其他寄生虫。
After the demonstration of blocking antibodies during rat experimental schistosomiasis, the existence of such factors was investigated in human schistosomiasis. The depletion, in sera from Schistosoma mansoni-infected patients, of a given isotype (IgM) either by protein A-Sepharose (PAS) absorption or by fast protein liquid chromtography (FPLC) induced a significant increase in IgG-mediated killing of S. mansoni schistosomula by human eosinophils. Inhibition experiments showed that IgM-enriched fractions (PAS effluents) were able to inhibit eosinophil-dependent cytotoxicity mediated by IgG fractions (total sera or PAS eluates). Both IgG and IgM antibodies from infected human sera immunoprecipitated antigens of 30,000-40,000 Mr in the labeled detergent extracts of schistosomulum surface. The specificity of IgG and IgM for the 38,000 Mr antigen was suggested by competition experiments using two radiolabeled mAbs (IPLSm1, IPLSm3) directed against this antigen. Moreover, crossinhibition between IgG and IgM antibodies for the Mr 38,000 antigen could be directly demonstrated. The in vivo relevance of such IgM blocking antibodies in the context of human immunity to schistosomiasis was evaluated in two groups of children classified as resistant or susceptible to posttreatment reinfection. IgM antibodies specifically directed against the 38,000 Mr antigen were measured by a capture assay. The mean levels of IgM antibodies were significantly higher in the susceptible than in the resistant group both before and after treatment. These results are consistent with the idea that immunity to schistosomiasis could be attributable not only to the existence of antibodies with defined effector function, but also to the absence of blocking antibodies. The description of the existence in human schistosomiasis of antibody isotypes blocking the effector response against defined surface targets might lead to a new understanding of the mechanisms regulating immunity to reinfection against schistosomes and possibly other parasites.