Anti-desmoglein (Dsg) 1 and Dsg3 IgG autoantibodies in pemphigus foliaceus and pemphigus vulgaris cause blisters through loss of desmosomal adhesion. It is controversial whether blister formation is due to direct inhibition of Dsg, intracellular signaling events causing desmosome destabilization, or both. Recent studies show that heterophilic binding between Dsg and desmocollin (Dsc) is the fundamental adhesive unit of desmosomes. To eliminate cellular contributions to potential pathogenicity of pemphigus antibodies, bead assays coated with recombinant Dsg1, Dsc1, Dsg3, or Dsc3 ectodomains were developed. A mixture of Dsg beads and Dsc beads formed large aggregates, confirming that the heterophilic binding is dominant. The pathogenic anti-Dsg1 and anti-Dsg3 mAbs, which bind the transadhesive interface, blocked the aggregation of Dsg1/Dsc1 and Dsg3/Dsc3 beads, respectively, whereas nonpathogenic mAbs did not. All sera tested from eight patients with pemphigus foliaceus and eight patients with mucosal pemphigus vulgaris with active disease inhibited the adhesion of Dsg1/Dsc1 and Dsg3/Dsc3 beads, respectively. When paired sera obtained from seven patients with pemphigus foliaceus and six patients with pemphigus vulgaris in active disease and remission were compared, the former inhibited aggregation better than the latter. These findings strongly suggest that steric hindrance of heterophilic transinteraction between Dsg and Dsc is important for disease pathology in both pemphigus foliaceus and pemphigus vulgaris.

天疱疮天疱疮和寻常型天疱疮中的抗桥粒芯蛋白（Dsg）1和Dsg3 IgG自身抗体会通过桥粒粘连的丧失而引起水泡。水泡的形成是否是由于直接抑制Dsg，引起桥粒不稳定的细胞内信号转导事件，还是两者都引起争议。最近的研究表明，Dsg和桥粒胶蛋白（Dsc）之间的亲和性结合是桥粒的基本粘附单元。为消除细胞对天疱疮抗体潜在致病性的影响，开发了用重组Dsg1，Dsc1，Dsg3或Dsc3胞外域包被的微珠测定法。Dsg珠粒和Dsc珠粒的混合物形成大的聚集体，这证实了嗜异性结合是主要的。病原性抗Dsg1和抗Dsg3单抗结合跨粘连界面，分别阻止了Dsg1 / Dsc1和Dsg3 / Dsc3珠的聚集，而非致病性mAb则没有。来自八名叶天疱疮患者和八名患有活动性疾病的粘膜天疱疮患者的所有血清测试分别抑制了Dsg1 / Dsc1和Dsg3 / Dsc3珠的粘附。比较从7例叶天疱疮患者和6例寻常性天疱疮患者在活动性疾病和缓解中获得的配对血清，前者抑制聚集的作用优于后者。这些发现强烈表明，Dsg和Dsc之间的异位相互作用的空间位阻对叶枯萎病天疱疮和寻常性天疱疮都非常重要。八名患有天疱疮的天疱疮患者和八名患有活动性疾病的粘膜天疱疮患者的所有血清均分别抑制了Dsg1 / Dsc1和Dsg3 / Dsc3珠的粘附。比较从7例叶天疱疮患者和6例寻常性天疱疮患者在活动性疾病和缓解中获得的配对血清，前者抑制聚集的作用优于后者。这些发现强烈表明，Dsg和Dsc之间的异位相互作用的空间位阻对叶枯萎病天疱疮和寻常性天疱疮都非常重要。八名患有天疱疮的天疱疮患者和八名患有活动性疾病的粘膜天疱疮患者的所有血清均分别抑制了Dsg1 / Dsc1和Dsg3 / Dsc3珠的粘附。比较从7例叶天疱疮患者和6例寻常性天疱疮患者在活动性疾病和缓解中获得的配对血清，前者抑制聚集的作用优于后者。这些发现强烈表明，Dsg和Dsc之间的异位相互作用的空间位阻对叶枯萎病天疱疮和寻常性天疱疮都非常重要。比较了7例叶天疱疮患者和6例寻常性天疱疮患者在活动性疾病和缓解方面的配对血清，前者的抑制作用优于后者。这些发现强烈表明，Dsg和Dsc之间的异位相互作用的空间位阻对叶枯萎病天疱疮和寻常性天疱疮都非常重要。比较从7例叶天疱疮患者和6例寻常性天疱疮患者在活动性疾病和缓解中获得的配对血清，前者抑制聚集的作用优于后者。这些发现强烈表明，Dsg和Dsc之间的异位相互作用的空间位阻对于叶枯萎病天疱疮和寻常性天疱疮都非常重要。