Pathogenicity of IgG subclass autoantibodies to type VII collagen: induction of dermal-epidermal separation

Journal of Autoimmunity
A ReckeDetlef Zillikens

Abstract

In different autoimmune diseases, tissue damage is mediated by the Fc portion of autoantibodies. These include autoimmunity to type VII collagen, a major hemidesmosomal skin constituent, where autoantibodies activate both complement and leukocytes, leading to separation within the dermal-epidermal junction. Fc-dependent effector functions differ among IgG subclasses. To elucidate the still controversial role of IgG subclasses in the pathogenesis of autoimmunity to type VII collagen, we generated a unique set of V gene-matched recombinant chimeric anti-type VII collagen autoantibodies of the four human IgG subclasses. Binding specificities and avidities of all four autoantibodies were comparable. Using ex vivo models, our results demonstrate that a monoclonal autoantibody is sufficient to activate complement and to induce dermal-epidermal separation. However, only IgG1 and IgG3, but not IgG2 and IgG4 against type VII collagen, were pathogenic in our ex vivo model systems. To our knowledge, this is the first time that a full-length recombinant disease-related human autoantibody has been investigated. Our results demonstrate the usefulness of recombinant antibody technology to dissect the contribution of F(ab')(2) and Fc portions ...Continue Reading

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Citations

Nov 2, 2014·American Journal of Clinical Dermatology·James J ContestableJon H Meyerle
Feb 19, 2015·Journal of Immunotoxicology·So-Nam KimYong Heo
Oct 17, 2015·Expert Review of Clinical Immunology·Ralf Ludwig
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Jun 2, 2012·Journal of Autoimmunity·Misa HiroseEnno Schmidt
Jun 3, 2015·Journal of Autoimmunity·Andreas ReckeUNKNOWN German AIBD Genetic Study Group
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Jul 3, 2013·Experimental Dermatology·Mattias Collin, Marc Ehlers

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