Recombinant human IgA1 and IgA2 autoantibodies to type VII collagen induce subepidermal blistering ex vivo.

Abstract

Subepidermal autoimmune blistering dermatoses (AIBD) are prototypic autoantibody-mediated diseases. In epidermolysis bullosa acquisita (EBA), an autoimmune disease with severe and chronic skin blistering, autoantibodies are directed against type VII collagen. IgG is the predominant autoantibody isotype of EBA, the pathogenicity of which has been demonstrated in a variety of in vivo and ex vivo disease models. In contrast, there is not much evidence for the pathogenicity of IgA, which may appear as the only autoantibody isotype in some EBA patients. To investigate the pathogenic potential of IgA autoantibodies, we generated chimeric V gene-matched human IgA1, IgA2, and control IgG1 autoantibodies directed against type VII collagen. Immobilized immune complexes containing the rIgA1 and rIgA2 autoantibodies induced the dose-dependent release of reactive oxygen species from neutrophil granulocytes, a precondition for blister formation. Moreover, both rIgA1 and rIgA2 induced leukocyte-dependent dermal-epidermal separation in cryosections of human skin. In contrast with rIgG1, neither rIgA1 nor rIgA2 was capable of inducing complement deposition at the dermal-epidermal junction. Because complement activation is a prerequisite for blister induction, this lack of function compared with IgG1 may be compensated for by the stronger activation of neutrophil granulocytes by both IgA1 and IgA2. For IgG-mediated AIBD, immunoadsorption therapy is a convenient treatment modality for the removal of pathogenic autoantibodies, particularly in treatment-resistant cases. The results of this study show the pathogenic potential of IgA autoantibodies and support the development of adsorber matrices for IgA-mediated AIBD.

• Authors: Andreas Recke, Luisa M Trog, Hendri H Pas, Artem Vorobyev, Aida Abadpour, Marcel F Jonkman, Ger van Zandbergen, Claudia Kauderer, Detlef Zillikens, Gestur Vidarsson, Ralf J Ludwig
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 4 Pg. 1600-8 (Aug 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25024393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Autoantibodies
• Collagen Type VII
• Immunoglobulin A
• Immunoglobulin G
• Reactive Oxygen Species

Topics

• Autoantibodies (immunology)
• Blister (immunology)
• Cell Line
• Collagen Type VII (immunology)
• Complement Activation (immunology)
• Epidermolysis Bullosa Acquisita (immunology, pathology)
• HEK293 Cells
• Humans
• Immunoglobulin A (immunology)
• Immunoglobulin G (immunology)
• Inflammation (immunology)
• Molecular Sequence Data
• Neutrophils (immunology)
• Reactive Oxygen Species (immunology)
• Skin (immunology, pathology)