In a study appearing online on March 24, in advance of the April 1 print edition of the Journal of Clinical Investigation, Aimee Payne and colleagues from the University of Pennsylvania analyze the pathogenic antibodies to desmogleins in a patient with pemphigus in order to make progress into the development of more targeted therapy for this disease.
The authors engineered antibodies like those found in the pemphigus patient, then showed that the antibodies inactivate desmogleins and have harmful effects on skin cells in culture. When transferred to mice, the antibodies induced blisters like those seen in pemphigus patients. The researchers also identified the regions on the antibody that cause the autoimmune response.
This data is the first to report the successful cloning of human antibodies in pemphigus that reproduce the disease in vitro and in mice, and offer a new opportunity for the development of therapies to treat this deadly disease. These results add to our understanding of cell adhesion in general and the pathogenesis of pemphigus disease.
TITLE: Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display
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