IgG subclass analysis and IgG4 depletion therapy for pemphigus

天疱疮是一种自身免疫性水疱疾病，由循环抗体引起的抗粘粒蛋白（Dsg），它是表皮细胞-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特异性自身抗体在IgG4中富集。此外，天疱疮患者血清总IgG4含量丰富。此外，在角质细胞分离实验中，天疱疮血清中IgG4的消耗降低了致病性。活动期天疱疮患者的dsg特异性IgG4血清中位浓度显著高于缓解期患者（p=0.04）。与未受影响的个体相比，天疱疮患者的记忆B细胞群中表面igg4阳性细胞丰富。IgG4可以通过免疫吸附或通过选择性消耗表面IgG4记忆B细胞来消耗，并且我们已经证明可以结合并因此基于表面IgG4表达的潜在靶向。

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.