Susani M, Schulze M, Exner M, Kerjaschki D
Division of Ultrastructural Pathology and Cell Biology, University of Vienna, Austria.
Am J Pathol. 1994 Apr;144(4):807-19.
Passive Heymann nephritis is an experimental rat model of human membranous nephropathy induced by injection of antisera against crude renal cortical fractions such as Fx1A or rat tubular microvilli. This results in the formation of subepithelial immune deposits, the activation of the C5b-9 membrane attack complex of complement, and severe proteinuria. While the formation of immune deposits is attributed to in situ immune complex formation with antibodies specific for the gp330-Heymann nephritis antigenic complex (HNAC), activation of complement and proteinuria appear to be caused by at least one additional antibody species present in anti-Fx1A sera. We have separated by affinity absorption polyspecific antisera against Fx1A and rat microvilli into one IgG fraction directed specifically against microvillar proteins (anti-Fx1A-prot) and another IgG fraction specific for glycolipids (ant-Fx1A-lip) of tubular microvilli. When injected into rats, the anti-Fx1A-prot fraction induced immune deposits but failed to activate complement or produce proteinuria, similar to results obtained with affinity-purified anti-gp330 IgG. When the antibodies of the anti-Fx1A-lip fraction were injected alone they did not bind to glomeruli. By contrast, when the IgGs specific for the Fx1A-prot fraction (or for gp330-HNAC) were combined with those directed against the Fx1A-lip glycolipid preparation, immune deposits were formed, in situ complement activation was observed, and also proteinuria was induced. It is concluded that within anti-Fx1A and anti-microvillar sera there are at least two IgG fractions of relevance for the development of PHN: one directed against the gp330-HNAC complex which is responsible for the development of immune deposits, and a second specific for glycolipid antigen(s) which activate(s) the complement cascade.
被动性海曼肾炎是一种通过注射针对粗制肾皮质组分（如Fx1A或大鼠肾小管微绒毛）的抗血清诱导的人类膜性肾病实验大鼠模型。这会导致上皮下免疫沉积物的形成、补体C5b-9膜攻击复合物的激活以及严重蛋白尿。虽然免疫沉积物的形成归因于与gp330-海曼肾炎抗原复合物（HNAC）特异性抗体的原位免疫复合物形成，但补体激活和蛋白尿似乎是由抗Fx1A血清中存在的至少一种其他抗体种类引起的。我们通过亲和吸收将针对Fx1A和大鼠微绒毛的多特异性抗血清分离为一个特异性针对微绒毛蛋白的IgG组分（抗Fx1A-prot）和另一个特异性针对肾小管微绒毛糖脂的IgG组分（抗Fx1A-lip）。当注射到大鼠体内时，抗Fx1A-prot组分诱导免疫沉积物形成，但未能激活补体或产生蛋白尿，这与用亲和纯化的抗gp330 IgG获得的结果相似。当单独注射抗Fx1A-lip组分的抗体时，它们不会与肾小球结合。相比之下，当针对Fx1A-prot组分（或针对gp330-HNAC）的IgG与针对Fx1A-lip糖脂制剂的IgG结合时，会形成免疫沉积物，观察到原位补体激活，并且也会诱导蛋白尿。结论是，在抗Fx1A和抗微绒毛血清中，至少有两个IgG组分与被动性海曼肾炎的发展相关：一个针对gp330-HNAC复合物，负责免疫沉积物的形成；另一个针对糖脂抗原，可激活补体级联反应。
