If pemphigus vulgaris IgG are the cause of acantholysis, new IgG-independent mechanisms are the concause.
Pemphigus vulgaris (PV) is a disease of epidermal adhesion. Its pathogenesis is currently traced back to the action of autoantibodies against antigens located within the intercellular substance of keratinocytes, such as desmogleins and acetylcholine receptors. In the present paper, we sought to elucidate the non-IgG-mediated effects of PV sera on keratinocytes. Results showed that PV sera depleted of IgG were able to induce well-defined changes on keratinocyte morphology and metabolic activity. Indeed, PV IgG-free sera determined marked alterations on cell shape, accompanied by partial loss of keratinocyte-keratinocyte interactions within 48 h after treatment. Furthermore, PV IgG-depleted sera caused a sharp reduction of cell viability along with a less sustained weakening of intercellular adhesion strength. In light of the above findings, loss of cell-cell adhesion in PV occurs as a result of the cooperating action of both IgG and non-IgG-mediated mechanisms. These data have remarkable consequences on experimental models of PV and might open new "biological" approaches to its therapy. Thus, researchers are well advised that PV pathophysiology cannot be faithfully reproduced by leaving non-IgG serum factors out of consideration.
Cirillo
Nicola
N
Regional Center on Craniofacial Malformations-MRI, 1st School of Medicine and Surgery, II University of Naples, Naples, Italy. cirillo.sun@libero.it
Lanza
Michele
M
Femiano
Felice
F
Gaeta
Giovanni Maria
GM
De Rosa
Alfredo
A
Gombos
Fernando
F
Lanza
Alessandro
A
D000051:Acantholysis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002460:Cell Line; D048430:Cell Shape; D002470:Cell Survival; D051184:Desmoglein 3 / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007365:Intercellular Junctions; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010392:Pemphigus / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D044967:Serum / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G