Johansson C, Butkowski R, Swedenborg P, Alm P, Wieslander J
Department of Nephrology, University Hospital, Lund, Sweden.
Nephrol Dial Transplant. 1993;8(11):1205-10.
Goodpasture's syndrome is a very severe and aggressive autoimmune kidney disease. The patients' autoantibodies, which are pathogenic, are restricted to the C-terminal region of the alpha 3-chain of type IV collagen. In this paper we characterize an anti-type IV collagen antibody from a patient with a non-progressive form of glomerulonephritis. ELISA and immunoblotting were used to study the specificity of this patient's antibodies. The patient had high titres of antibodies restricted to the C-terminal region of the alpha 1-chain of type IV collagen. The antibody recognized an epitope hidden in the NC1 molecule which was fully exposed after denaturation or reduction. It was an IgG3 antibody composed of only lambda light chains, indicating that it has a potential to induce inflammatory damage and that it is probably monoclonal. This patient also had MPO-ANCA which were of IgG1 subclass. Our patient had no disease progression during the 5 years of treatment. Even though the anti-alpha 1 (IV) antibodies react with the same domain, but of a different chain of type IV collagen compared to the Goodpasture's antibodies, they do not induce any severe damage. It is thus uncertain if the anti-alpha 1 (IV) antibodies have any pathogenic role; the kidney damage might have been caused by the MPO-ANCA. The findings support the theory that the anti-alpha 3 (IV) antibody causes disease in Goodpasture's syndrome and that antibodies restricted to other subunits of the C-terminal region of type IV collagen are less harmful.
肺出血肾炎综合征是一种非常严重且进展迅速的自身免疫性肾脏疾病。患者的致病性自身抗体局限于IV型胶原α3链的C末端区域。在本文中，我们对一名患有非进行性肾小球肾炎患者的抗IV型胶原抗体进行了特征分析。采用酶联免疫吸附测定（ELISA）和免疫印迹法研究了该患者抗体的特异性。该患者具有高滴度的抗体，这些抗体局限于IV型胶原α1链的C末端区域。该抗体识别一个隐藏在NC1分子中的表位，该表位在变性或还原后会完全暴露。它是一种仅由λ轻链组成的IgG3抗体，表明它有诱导炎症损伤的潜力，并且可能是单克隆的。该患者还具有IgG1亚类的髓过氧化物酶抗中性粒细胞胞浆抗体（MPO - ANCA）。在5年的治疗期间，我们的患者病情没有进展。尽管与肺出血肾炎综合征的抗体相比，抗α1（IV）抗体与IV型胶原不同链的相同结构域发生反应，但它们不会引起任何严重损伤。因此，抗α1（IV）抗体是否具有任何致病作用尚不确定；肾脏损伤可能是由MPO - ANCA引起的。这些发现支持了以下理论：抗α3（IV）抗体在肺出血肾炎综合征中导致疾病，而局限于IV型胶原C末端区域其他亚基的抗体危害较小。
