Ultrastructural studies of acantholysis induced in vivo by passive transfer of IgG from endemic pemphigus foliaceus (Fogo Selvagem)

Abstract

Intraperitoneal (IP) injections of IgG from patients with Endemic Pemphigus Foliaceus [Fogo Selvagem (FS)] cause acantholysis in BALB/c mice (JID. 85:538, 1985). The dynamic ultrastructural changes of FS IgG-induced acantholysis in mice are the subject of this study. FS IgG was injected IP into neonatal BALB/c mice. Skin and serum was studied at 0, 1, 3, 6, 12, 18, and 24 h post injection by immunofluorescence (IF), electron microscopy (EM), and immuno-EM. Binding of FS IgG in the intercellular spaces (ICS) of the basal cell layer was seen by IF within 1 h and was strongest at 12 h. IgG binding affected the spinous and granular cell layer by 12 h, then faded and remain localized only in the basal cell layer at 24 h. By immuno-EM, IgG binding was diffuse along the keratinocyte surface. Edema of the ICS in the basal cell layer was present at 1 h by EM. At 12 h, there was microvillous formation with intact desmosomes at the tip of the projections. Splitting of desmosomes (forming half desmosomes) and acantholysis primarily affecting the granular cell layer were most prominent between 12 and 24 h. The plaques of the half desmosomes gradually disappeared and tonofilaments retracted into the cytoplasm. Detaching keratinocytes showed vacuolization, swollen mitochondria, and internalization of intact desmosomes and half desmosomes (remnants of split desmosomes). This investigation shows that the ultrastructural changes observed in the epidermis of patients with FS can be duplicated in experimental animals by IP injection of FS IgG. Further, FS IgG may have direct effects on the assembly/disassembly of desmosomes.