Kohda Takayuki, Okada Shin-Ichi, Hayashi Atsushi, Kanzaki Susumu, Ninomiya Yoshifumi, Taki Masafumi, Sado Yoshikazu
Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan.
Kidney Int. 2004 Jul;66(1):177-86. doi: 10.1111/j.1523-1755.2004.00719.x.
To examine a subclass-effect relationship and a dose-effect relationship of autoantibodies in the rat antiglomerular basement membrane (GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) model, we injected homologous monoclonal antibodies against the NC1 domains of rat type IV collagen into inbred Wistar-Kyoto (WKY) rats.
Eight different autoantibodies from each of the IgG1, IgG2a, and IgG2b subclasses were established and administered to groups of four WKY rats at a dose of 300 microg/rat. To examine the dose-effect relationship, we administered 0 to 300 microg/rat of autoantibodies from each subclass to rats.
All IgG1 antibodies induced mild nephritis, whereas the IgG2a and IgG2b antibodies induced moderate to severe nephritis. Some IgG2a and IgG2b antibodies induced pulmonary hemorrhage as well. These antibodies were reactive with alpha3(IV)NC1, alpha4(IV)NC1, or alpha5(IV)NC1. The minimum dose of antibody required to induce nephritis was 30 microg/rat for IgG1, 3 microg/rat for IgG2a, and 1 microg/rat for IgG2b. At doses of 30 microg/rat or less, antibody deposition was generally restricted to the GBM. At doses of 100 microg/rat or greater, antibody deposition extended to both the GBM and tubular basement membrane (TBM). Pulmonary hemorrhage was observed only when a large amount of pulmonary hemorrhagic antibody was administered.
The severity of nephritis was dependent on both subclass and dose of autoantibodies. It becomes clear that pulmonary hemorrhage in anti-GBM nephritis is induced by autoantibodies.
为了研究大鼠抗肾小球基底膜（GBM）抗体诱导的肾小球肾炎（抗GBM肾炎）模型中自身抗体的亚类效应关系和剂量效应关系，我们将针对大鼠IV型胶原NC1结构域的同源单克隆抗体注射到近交系Wistar-Kyoto（WKY）大鼠体内。
分别从IgG1、IgG2a和IgG2b亚类中制备了8种不同的自身抗体，并以300μg/只的剂量给予每组4只WKY大鼠。为了研究剂量效应关系，我们将每个亚类的自身抗体以0至300μg/只的剂量给予大鼠。
所有IgG1抗体均诱导轻度肾炎，而IgG2a和IgG2b抗体诱导中度至重度肾炎。一些IgG2a和IgG2b抗体还诱导了肺出血。这些抗体与α3（IV）NC1、α4（IV）NC1或α5（IV）NC1发生反应。诱导肾炎所需的最低抗体剂量，IgG1为30μg/只，IgG2a为3μg/只，IgG2b为1μg/只。在30μg/只或更低的剂量下，抗体沉积通常仅限于GBM。在100μg/只或更高的剂量下，抗体沉积扩展至GBM和肾小管基底膜（TBM）。仅在给予大量肺出血性抗体时才观察到肺出血。
肾炎的严重程度取决于自身抗体的亚类和剂量。抗GBM肾炎中的肺出血显然是由自身抗体诱导的。
