Plaisier Emmanuelle, Borradori Luca, Hellmark Thomas, Wattiaux Marie-José, Flageul Béatrice, Mougenot Béatrice, Ronco Pierre
INSERM U489 and Department of Nephrology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.
Am J Kidney Dis. 2002 Sep;40(3):649-54. doi: 10.1053/ajkd.2002.34929.
Anti-glomerular basement membrane (GBM) nephritis is a rare disease induced by antibodies directed against alpha3(IV)NC1, the Goodpasture antigen. We report a patient with Crohn's disease who developed anti-GBM nephritis and the skin blistering disorder bullous pemphigoid, owing to distinct autoantibodies.
Frozen sections of skin and kidney biopsies were incubated with antisera specific for human IgG, IgA, IgM, fibrin, and C3. Reactivity of the patient's serum with GBM antigens was studied by Western blot using bovine solubilized type IV collagen and by enzyme-linked immunosorbent assays using alpha1(IV), alpha3(IV), and alpha5(IV)NC1 recombinant proteins. Reactivity studies against skin antigens were done by Western blot using human keratinocyte and dermal extracts and three recombinant forms of the bullous pemphigoid antigen180 (BP180, also called BPAG2 or type XVII collagen). The patient's serum was affinity fractionated on a (IV)NC1 column, and the bound and unbound fractions were analyzed for their reactivity against GBM and skin antigens.
The patient had deposits of IgG along the GBM and the epidermal basement membrane zone. Circulating IgG antibodies against alpha3(IV)NC1 were detected. The patient's autoantibodies immunoblotted the intracellular domain but not the extracellular domain of BP180. Reactivity of the patient's IgG with BP180 was found only in the unbound fraction of the serum.
The simultaneous development of a rare renal and skin autoimmune disorder, resulting from non-cross-reactive autoantibodies, suggests that a common triggering event could be responsible for the autoimmune injury.
抗肾小球基底膜（GBM）肾炎是一种由针对Goodpasture抗原α3（IV）NC1的抗体引起的罕见疾病。我们报告了一名克罗恩病患者，该患者由于不同的自身抗体而发生了抗GBM肾炎和皮肤水疱性疾病大疱性类天疱疮。
皮肤和肾活检的冰冻切片与针对人IgG、IgA、IgM、纤维蛋白和C3的抗血清孵育。通过使用牛可溶性IV型胶原的蛋白质印迹法以及使用α1（IV）、α3（IV）和α5（IV）NC1重组蛋白的酶联免疫吸附测定法研究患者血清与GBM抗原的反应性。使用人角质形成细胞和真皮提取物以及三种重组形式的大疱性类天疱疮抗原180（BP180，也称为BPAG2或XVII型胶原）通过蛋白质印迹法进行针对皮肤抗原的反应性研究。患者血清在（IV）NC1柱上进行亲和分级分离，并分析结合和未结合部分对GBM和皮肤抗原的反应性。
患者的IgG沿GBM和表皮基底膜带沉积。检测到循环抗α3（IV）NC1 IgG抗体。患者的自身抗体对BP180的细胞内结构域进行免疫印迹，但对其细胞外结构域未进行免疫印迹。仅在血清的未结合部分中发现患者的IgG与BP180有反应性。
由非交叉反应性自身抗体导致的一种罕见的肾脏和皮肤自身免疫性疾病同时发生，提示一个共同的触发事件可能是自身免疫损伤的原因。
