Stark J H, Smit J A, Neethling F A, Nortman P J, Myburgh J A
MRC Unit for Research in Organ Transplantation, Department of Surgery, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Transplantation. 1991 Dec;52(6):1072-8. doi: 10.1097/00007890-199112000-00025.
Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.
对未来供体器官短缺加剧的预测引发了对异种移植兴趣的再度兴起。我们系统地评估了人类与南非大狒狒的免疫相容性,旨在通过仔细的免疫筛选缩小一致性差距。异种移植中主要血型相容性的必要性现已确立。虽然南非大狒狒中不存在O型通用供体,但A组(45%)、B组(15%)和AB组(40%)的比例较高。使用人抗血清无法精确界定南非大狒狒的组织相容性抗原。这不一定意味着物种间缺乏同源性,因为我们已证明众多抗人单克隆抗体与南非大狒狒白细胞存在特异性交叉反应。正常人类对南非大狒狒(东非狒狒)的红细胞不表现出预先形成的凝集素,但偶尔会发现细胞毒性抗体。同种致敏患者的血清可能含有交叉反应性血凝素、白细胞凝集素和补体依赖性细胞毒性抗体。通过流式细胞术证明了人免疫球蛋白G和M与南非大狒狒靶标的结合。很容易找到IgG亚类抗体的阴性交叉配型组合,但同种致敏患者的IgM抗体作用具有多特异性。淋巴细胞介导的细胞毒性的体外评估表明,物种间预先形成的细胞免疫很少见。混合淋巴细胞培养中人淋巴细胞对异种抗原刺激的反应呈正态分布,从而能够选择低反应性组合。筛查病毒,尤其是HTLV - 1和柯萨奇B - L34病毒,很重要。这些发现表明一致性程度比之前怀疑的要高。