IgG subclass analysis and IgG4 depletion therapy for pemphigus

天疱疮的 IgG 亚类分析和 IgG4 去除疗法

• 批准号: 24791175
• 负责人: FUNAKOSHI Takeru
• 金额: $ 2.66万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24791175/
• 关键词: 天疱瘡; IgG4; 治療

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.

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。