| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Dermatology, University of California at Davis, School of Medicine, Davis, California
Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by cell-cell detachment within the stratified epithelium (acantholysis) caused by IgG autoantibodies. Intravenous immunoglobulin (IVIg) therapy effectively treats PV, but the mechanism is not fully understood. To further understand acantholysis and the efficacy of IVIg, we measured effects of IgG fractions from PV patients on keratinocyte death processes. Using IgGs from representative PV patients who improved with IVIg, we identified apoptotic and oncotic signaling pathways in in vitro and in vivo PV models. We identified two groups of PV patients, each producing autoantibodies activating predominantly either apoptotic or oncotic cell death pathway. Experimental treatments with caspase 3 or calpain inhibitors demonstrated that PV IgGs induced acantholysis through both pathways. Upstream, the apoptotic signaling involved activation of caspases 8 and 3 and up-regulation of Fas ligand mRNA, whereas calpain-mediated cell death depended on elevated intracellular free Ca2+. IVIg reduced PV IgG-mediated acantholysis and cell death and up-regulated the caspase inhibitor FLIP and the calpain inhibitor calpastatin. These results indicate that in different PV patients, IgG-induced acantholysis proceeds predominantly via distinct, yet complementary, pathways of programmed cell death differentially mediated by apoptosis and oncosis effectors, with IVIg protecting target cells by up-regulating endogenous caspase and calpain inhibitors.
This article has been cited by other articles:
 |
|
 |
|
  S. Marchenko, A. I. Chernyavsky, J. Arredondo, V. Gindi, and S. A. Grando Antimitochondrial Autoantibodies in Pemphigus Vulgaris: A MISSING LINK IN DISEASE PATHOPHYSIOLOGY J. Biol. Chem., February 5, 2010; 285(6): 3695 - 3704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Li, M. Zhao, J. Wang, Z. Liu, and L. A. Diaz Involvement of the Apoptotic Mechanism in Pemphigus Foliaceus Autoimmune Injury of the Skin J. Immunol., January 1, 2009; 182(1): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schmidt, J. Gutberlet, D. Siegmund, D. Berg, H. Wajant, and J. Waschke Apoptosis is not required for acantholysis in pemphigus vulgaris Am J Physiol Cell Physiol, January 1, 2009; 296(1): C162 - C172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lanza, N. Cirillo, R. Rossiello, M. Rienzo, L. Cutillo, A. Casamassimi, F. de Nigris, C. Schiano, L. Rossiello, F. Femiano, et al. Evidence of Key Role of Cdk2 Overexpression in Pemphigus Vulgaris J. Biol. Chem., March 28, 2008; 283(13): 8736 - 8745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Chernyavsky, J. Arredondo, T. Piser, E. Karlsson, and S. A. Grando Differential Coupling of M1 Muscarinic and {alpha}7 Nicotinic Receptors to Inhibition of Pemphigus Acantholysis J. Biol. Chem., February 8, 2008; 283(6): 3401 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Blank, L. Anafi, G. Zandman-Goddard, I. Krause, S. Goldman, E. Shalev, R. Cervera, J. Font, M. Fridkin, H.-J. Thiesen, et al. The efficacy of specific IVIG anti-idiotypic antibodies in antiphospholipid syndrome (APS): trophoblast invasiveness and APS animal model Int. Immunol., July 1, 2007; 19(7): 857 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Chernyavsky, J. Arredondo, Y. Kitajima, M. Sato-Nagai, and S. A. Grando Desmoglein Versus Non-desmoglein Signaling in Pemphigus Acantholysis: CHARACTERIZATION OF NOVEL SIGNALING PATHWAYS DOWNSTREAM OF PEMPHIGUS VULGARIS ANTIGENS J. Biol. Chem., May 4, 2007; 282(18): 13804 - 13812. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
