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Originally published online as doi:10.2353/ajpath.2007.061212 on April 13, 2007

Published online before print April 13, 2007
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(American Journal of Pathology. 2007;170:2009-2018.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061212

The Cartilage Matrix Protein Subdomain of Type VII Collagen Is Pathogenic for Epidermolysis Bullosa Acquisita

Mei Chen*, Arvin Doostan*, Pubali Bandyopadhyay*, Jennifer Remington*, Xinyi Wang*, Yingping Hou*, Ziu Liu{dagger} and David T. Woodley*

From the Department of Dermatology,* The Keck School of Medicine at the University of Southern California, Los Angeles, California; and the Department of Dermatology,{dagger} University of North Carolina, Chapel Hill, North Carolina

Epidermolysis bullosa acquisita (EBA) is an acquired bullous disease of the skin characterized by IgG autoantibodies against type VII (anchoring fibril) collagen. We previously defined four immunodominant antigenic epitopes within the noncollagenous 1 (NC1) domain of type VII collagen. In this study, we produced an additional recombinant fusion protein from the NC1 domain corresponding to the N-terminal 227 amino acids (residues 1 to 227), which contains homology with cartilage matrix protein (CMP). Using enzyme-linked immunosorbent assay and immunoblot analysis, we tested sera from EBA patients (n = 32), bullous systemic lupus erythematosus patients (n = 3), bullous pemphigoid patients (n = 15), and normal humans (n = 12). Twenty-six of 32 EBA sera and two of three bullous systemic lupus erythematosus sera reacted with the CMP domain, whereas none of the control sera did. Affinity-purified anti-CMP EBA antibodies injected into hairless mice produced the clinical, histological, immunological, and ultrastructural features of EBA. F(ab')2 fragments generated from anti-CMP EBA autoantibodies did not induce disease. Our studies provide the first evidence that EBA autoantibodies to the CMP subdomain of NC1 are pathogenic and induce blister formation. This is the first antigenic epitope on type VII collagen demonstrated to be a pathogenic target for EBA autoantibodies.




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