期刊
CELL REPORTS
卷 28, 期 4, 页码 909-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.06.066
关键词
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类别
资金
- NIH (Human Immunology Pilot award) [U19 AI057266]
- International Pemphigus and Pemphigoid Foundation
- Charles and Daneen Stiefel Scholar Award from the Dermatology Foundation
- Deutsche Forschungsgemeinschaft [FOR 2497 PEGASUS]
- National Center for Advancing Translational Sciences of the NIH [TL1TR001880]
Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering sores on skin and mucosal membranes, caused by autoantibodies primarily targeting the cellular adhesion protein, desmoglein-3 (Dsg3). To better understand how Dsg3-specific autoantibodies develop and cause disease in humans, we performed a cross-sectional study of PV patients before and after treatment to track relevant cellular responses underlying disease pathogenesis, and we provide an in-depth analysis of two patients by generating a panel of mAbs from single Dsg3-specific memory B cells (MBCs). Additionally, we analyzed a paired sample from one patient collected 15-months prior to disease diagnosis. We find that Dsg3-specific MBCs have an activated phenotype and show signs of ongoing affinity maturation and clonal selection. Monoclonal antibodies (mAbs) with pathogenic activity primarily target epitopes in the extracellular domains EC1 and EC2 of Dsg3, though they can also bind to the EC4 domain. Combining antibodies targeting different epitopes synergistically enhances in vitro pathogenicity.
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