Serum from pemphigus vulgaris reduces desmoglein 3 half-life and perturbs its de novo assembly to desmosomal sites in cultured keratinocytes.
Defects of cell-cell adhesion underlie disruption of epithelial integrity observed in patients with pemphigus vulgaris (PV), an autoimmune disease characterized by severe mucosal erosions and skin blisters. Pathogenic PV autoantibodies found in patients' sera target desmoglein 3 (Dsg3), a major component of the desmosome, but how does this phenomenon affect Dsg-dependent adhesion and lead to acantholysis still remains controversial. Here, we show that PV serum determines a reduction of Dsg3 half-life in HaCaT keratinocytes, although the total amount of Dsg3 remains unchanged. Immunofluorescence studies suggest that PV IgG exert their effect prevalently by binding non-desmosomal Dsg3 without causing its massive internalization. Furthermore, PV IgG targeting desmosome-assembled Dsg3 do not induce depletion of Dsg3 from the adhesion sites. Conversely, incorporation of PV IgG-Dsg3 complexes into new forming desmosomes appears perturbed. With our study, the basic biochemical changes of Dsg3 in an in vitro model of PV have been defined.
Cirillo
Nicola
N
Regional Center on Craniofacial Malformations-MRI, Department of Odontostomatology; 1st School of Medicine and Surgery, Second University of Naples, Via Luigi De Crecchio 7, 80138 Naples, Italy. nicola.cirillo@unina2.it
Femiano
Felice
F
Gombos
Fernando
F
Lanza
Alessandro
A
D001323:Autoantibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D051184:Desmoglein 3 / Q000187:drug effects* / Q000378:metabolism*; D003896:Desmosomes / Q000187:drug effects* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology; D044967:Serum / Q000276:immunology*
D001323:Autoantibodies; D051184:Desmoglein 3; D007074:Immunoglobulin G