detailed characterization of autoantibodies in paraneoplastic pemphigus by phage display

为了研究双亲瘤性天疱疮（PNP）的发病机制，我们利用噬菌体展示技术克隆了PNP患者的单克隆抗dsg3抗体。我们分离到20个独特的dsg3反应单抗，并根据氨基酸序列将其分为4组。致病性试验表明，三种抗体在水疱形成中表现出不同效力的致病性。表位定位显示，这些致病性单抗结合了Dsg3细胞外区域中部Ca（2+）依赖性构象表位。这些单克隆抗体反映了PNP中抗dsg3抗体独特的多克隆性质，是详细研究PNP中水疱形成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.