|Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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.