detailed characterization of autoantibodies in paraneoplastic pemphigus by phage display

为探讨副肿瘤性天疱疮(PNP)的发病机制，我们用噬菌体展示技术克隆了一例PNP患者的抗Dsg3单抗。我们分离了20株独有的Dsg3反应性单抗，并根据氨基酸序列将其分为四组。致病试验表明，三种抗体在水泡形成过程中表现出不同的致病活性。表位定位显示，这些致病单抗结合在Dsg3胞外区中部依赖于钙离子的构象表位。这些单抗反映了PNP中抗Dsg3抗体的独特的多克隆特性，是详细研究PNP中水泡形成的病理生理机制的重要工具。

To study the pathogenic mechanism of pareneoplastic pemphigus(PNP), we used phage display to clone monoclonal anti-Dsg3 antibodies from a PNP patient. We isolated 20 unique Dsg3-reactive mAbs, which we classified into four groups according to amino acid sequence. Pathogenic assay showed that three antibodies displayed pathogenic activity in blister formation with different potencies. Epitope mapping showed that these pathogenic mAbs bound Ca(2+)-dependent conformational epitopes in the middle portion of the extracellular region of Dsg3. These mAbs reflect the unique polyclonal nature of anti-Dsg3 antibodies in PNP and represent an important tool for detailing the pathophysiological mechanisms of blister formation in PNP.