| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Recke, Andreas Ludwig, Ralf J. Trog, Luisa M. Vorobyev, Artem Jonkman, Marcel F. Zillikens, Detlef Pas, Hendri H. Abadpour, Aida Van Zandbergen, Ger Kauderer, Claudia Vidarsson, Gestur |
| Description |
Author Affiliation: Recke A ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Trog LM ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Pas HH ( Centre for Blistering Diseases, Department of Dermatology, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, the Netherlands); Vorobyev A ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Abadpour A ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Jonkman MF ( Centre for Blistering Diseases, Department of Dermatology, University Medical Centre Groningen, University of Groningen, Groningen 9700 RB, the Netherlands); van Zandbergen G ( Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, D-63225 Langen, Germany); Kauderer C ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Zillikens D ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany); Vidarsson G ( Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.); Ludwig RJ ( Department of Dermatology, University of Lübeck, D-23538 Lübeck, Germany) |
| 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. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-08-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Autoantibodies Immunology Blister Collagen Type Vii Epidermolysis Bullosa Acquisita Immunoglobulin A Cell Line Complement Activation Pathology Hek293 Cells Immunoglobulin G Inflammation Molecular Sequence Data Neutrophils Reactive Oxygen Species Skin Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
