Pemphigus is a deadly skin blistering disease that occurs when patients' produce antibodies that attack proteins in their own cells – called autoantibodies.
In pemphigus, the body mounts abnormal attacks on molecules called desmogleins, which normally hold skin cells together. When autoantibodies attack desmogleins, the cells separate from each other, causing lesions and blisters that do not heal. The disease is fatal if not treated. Current therapy for this disease involves non-specific immune system suppression.
In a study appearing online, 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.