Budhai L, Oh K, Davidson A
Department of Medicine, Albert Einstein College of Medicine, New York 10461, USA.
J Clin Invest. 1996 Oct 1;98(7):1585-93. doi: 10.1172/JCI118952.
The deposition of anti-dsDNA antibodies in the glomerulus is believed to play a critical role in the pathogenesis of nephritis in SLE. However, an absolute correlation between serum levels of anti-dsDNA antibodies and renal disease has not been found. Recently a glomerular binding assay (GBA) has been developed to detect IgG binding to isolated rat glomeruli. We have used the GBA to study sera from four groups of SLE patients: (A) + anti-dsDNA antibodies, active nephritis; (B) - anti-dsDNA antibodies, active nephritis; (C) + anti-dsDNA antibodies, no nephritis; and (D) - anti-dsDNA antibodies, no nephritis. The serum anti-dsDNA antibodies in group A and group C patients could not be distinguished on the basis of isotype, charge, or cross-reactivity with histones. Nevertheless, the mean intensity of glomerular immunofluorescence was significantly higher in group A than in the three other patient groups and distinguished between patients with serum anti-dsDNA antibodies who had nephritis and those without clinically apparent nephritis. GBA reactivity was unaffected by DNase treatment of sera, but was partially inhibited by preincubation with dsDNA. These findings are consistent with the hypothesis that some anti-dsDNA antibodies cross-react with glomerular components and that the presence of this cross-reactivity is associated with, and may be responsible for, the development of nephritis. In addition, we have identified a group of SLE patients with renal disease and typical renal histopathology and immune deposits who do not have serum anti-dsDNA antibodies or antibodies that directly bind to glomeruli in the GBA. The mechanism of renal immune deposition in these patients remains to be determined.
抗双链DNA抗体在肾小球中的沉积被认为在系统性红斑狼疮肾炎的发病机制中起关键作用。然而，尚未发现血清抗双链DNA抗体水平与肾脏疾病之间存在绝对相关性。最近开发了一种肾小球结合试验（GBA）来检测IgG与分离的大鼠肾小球的结合。我们使用GBA研究了四组系统性红斑狼疮患者的血清：（A）抗双链DNA抗体阳性，活动性肾炎；（B）抗双链DNA抗体阴性，活动性肾炎；（C）抗双链DNA抗体阳性，无肾炎；（D）抗双链DNA抗体阴性，无肾炎。A组和C组患者的血清抗双链DNA抗体在同种型、电荷或与组蛋白的交叉反应性方面无法区分。然而，A组肾小球免疫荧光的平均强度明显高于其他三组患者，并且区分了有血清抗双链DNA抗体的肾炎患者和无临床明显肾炎的患者。血清经DNA酶处理后，GBA反应性不受影响，但与双链DNA预孵育可部分抑制该反应性。这些发现与以下假设一致，即一些抗双链DNA抗体与肾小球成分发生交叉反应，并且这种交叉反应的存在与肾炎的发生有关，可能是肾炎发生的原因。此外，我们还确定了一组患有肾脏疾病、具有典型肾脏组织病理学和免疫沉积物的系统性红斑狼疮患者，他们没有血清抗双链DNA抗体或在GBA中直接与肾小球结合的抗体。这些患者肾脏免疫沉积的机制仍有待确定。
