IgG subclass analysis and IgG4 depletion therapy for pemphigus

天疱疮是一种自身免疫性水疱性疾病，由循环中抗桥粒芯糖蛋白（Dsg）的抗体引起，Dsg是表皮中的细胞-细胞粘附蛋白。我们最近建立了抗Dsg IgG亚类ELISA方法，我们发现Dsg特异性自身抗体富集在IgG 4中。此外，天疱疮患者血清中总IgG 4富集。此外，天疱疮血清的IgG 4消耗降低了角质形成细胞解离试验中的致病性。与缓解期患者相比，活动期天疱疮患者中Dsg特异性IgG 4的中位血清浓度显著更高（p=0.04）。与未受影响的个体相比，天疱疮患者记忆B细胞群中表面IgG 4阳性细胞富集。IgG 4可通过免疫吸附或选择性耗竭表面IgG 4记忆B细胞而耗竭，我们已经证明可以结合，因此基于表面IgG 4表达可能具有靶向作用。

Pemphigus is an autoimmune blistering disease caused by circulating antibodies against desmogleins (Dsg) which are cell-cell adhesion protein in the epidermis. We recently established anti-Dsg IgG subclass ELISA method and we showed that Dsg-specific autoantibodies are enriched in IgG4. Addition to that total serum IgG4 was enriched in patients with pemphigus. Furthermore, IgG4 depletion of pemphigus sera reduced pathogenicity in a keratinocyte dissociation assay. The median serum concentration of Dsg-specific IgG4 was significantly higher in pemphigus patients during active disease compared to patients in remission(p=0.04). Memory B cell populations were enriched for surface-IgG4 positive cells in pemphigus compared to unaffected individuals.IgG4 could be depleted by immunoadsorption or by selective depletion of surface-IgG4 memory B cells, and which we have shown can be bound and hence potentially targeted based on surface IgG4 expression.