The α5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency

被引:50
作者
Ghohestani, RF
Hudson, BG
Claudy, A
Uitto, J
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Jefferson Inst Mol Med, Immunodermatol Unit, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA
[3] Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA
[4] Univ Lyon 1, E Herriot Hosp, Dept Dermatol, F-69437 Lyon, France
关键词
D O I
10.1074/jbc.275.21.16002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha 5(TV) 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 matric including type XVII collagen, type VII collagen, or the alpha 3, beta 3, and gamma 2 chains of laminin 5. Preincubation of the serum with recombinant alpha 5(IV)NC1 domain of type IV collagen abolished immunoreactivity with the 185-kDa antigen. The serum reacted specifically with the alpha 5(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 alpha 5(IV) collagen chain. This study provided for the first time unambiguous evidence for the alpha 5(IV) collagen chain as the target antigen in a novel autoimmune disease characterized by skin and renal involvement.
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页码:16002 / 16006
页数:5
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