The alpha 5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency.
The alpha 5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency.
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发表时间：
2000
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通讯作者：
R. Ghohestani;B. Hudson;A. Claudy;J. Uitto
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作者：
R. Ghohestani;B. Hudson;A. Claudy;J. Uitto
我们描述了一种新的自身免疫性疾病，其特征是严重的表皮下大疱性皮疹和肾功能不全与IgG自身抗体针对NC 1结构域的α 5（IV）胶原蛋白链。体内IgG和C3的沉积物被发现沿着皮肤病变的真皮-表皮交界处。通过使用患者自身抗体对候选抗原进行免疫化学分析来确定靶抗原的身份。患者的IgG自身抗体与185-kDa多肽反应，该多肽不同于细胞外基质的已知自身抗原，包括XVII型胶原、VII型胶原或层粘连蛋白5的α 3、β 3和γ 2链。血清与IV型胶原的重组α 5（IV）NC 1结构域的预孵育废除与185-kDa抗原的免疫反应性。通过Western blot和酶联免疫吸附测定分析，血清与IV型胶原的六个NC 1结构域中的α 5（IV）NC 1特异性反应。患者的自身抗体与正常皮肤和肾小球反应，但不与Alport综合征患者的皮肤和肾小球反应，其中基底膜缺乏α 5（IV）胶原蛋白链。这项研究首次提供了明确的证据，证明α 5（IV）胶原蛋白链是一种以皮肤和肾脏受累为特征的新型自身免疫性疾病的靶抗原。
We describe a novel autoimmune disease characterized by severe subepidermal bullous eruptions and renal insufficiency with IgG autoantibodies directed against the NC1 domain of the alpha5(IV) collagen chain. In vivo deposits of IgG and C3 were found along the dermal-epidermal junction of skin lesions. The identity of the target antigen was determined by immunochemical analyses of candidate antigens using the patients' autoantibodies. The patients' IgG autoantibodies reacted with a 185-kDa polypeptide that was distinguished from the known autoantigens of the extracellular matrix including type XVII collagen, type VII collagen, or the alpha3, beta3, and gamma2 chains of laminin 5. Preincubation of the serum with recombinant alpha5(IV)NC1 domain of type IV collagen abolished immunoreactivity with the 185-kDa antigen. The serum reacted specifically with the alpha5(IV)NC1, among the six NC1 domains of type IV collagen, by Western blot and enzyme-linked immunosorbent assay analyses. The patients' autoantibodies reacted with normal skin and renal glomerulus but not with skin and glomerulus of a patient with Alport syndrome in which the basement membranes are devoid of the alpha5(IV) collagen chain. This study provided for the first time unambiguous evidence for the alpha5(IV) collagen chain as the target antigen in a novel autoimmune disease characterized by skin and renal involvement.