|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 38, 29466-29476, September 22, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Dermatology, University of California at
Davis, Sacramento, California 95817
Because pemphigus vulgaris (PV) IgGs adsorbed on
the rDsg3-Ig-His baculoprotein induced blisters in neonatal mice, it
was proposed that anti-desmoglein 3 (Dsg 3) autoantibody causes PV. However, we found that rDsg3-Ig-His absorbs autoantibodies to different
antigens, including a non-Dsg 3 keratinocyte protein of 130 kDa. This
prompted our search for novel targets of PV autoimmunity. The PV IgG
eluted from a 75-kDa keratinocyte protein band both stained epidermis
in a pemphigus-like pattern and induced acantholysis in keratinocyte
monolayers. Screening of a keratinocyte The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF230929.
Pemphigus Vulgaris Antibody Identifies Pemphaxin
A NOVEL KERATINOCYTE ANNEXIN-LIKE MOLECULE BINDING
ACETYLCHOLINE*
gt11 cDNA library
with this antibody identified clones carrying cDNA inserts encoding
a novel molecule exhibiting ~40% similarity with annexin-2, named
pemphaxin (PX). Recombinant PX (rPX-His) was produced in
Escherichia coli M15 cells, and, because annexins can act
as cholinergic receptors, its conformation was tested in a cholinergic
radioligand binding assay. rPX-His specifically bound
[3H]acetylcholine, suggesting that PX is one of the
keratinocyte cholinergic receptors known to be targeted by
disease-causing PV antibodies. Preabsorption of PV sera with rPX-His
eliminated acantholytic activity, and eluted antibody
immunoprecipitated native PX. This antibody alone did not cause skin
blisters in vivo, but its addition to the preabsorbed PV
IgG fraction restored acantholytic activity, indicating that
acantholysis in PV results from synergistic action of antibodies to
different keratinocyte self-antigens, including both acetylcholine
receptors and desmosomal cadherins.
*
This work was supported by the International Pemphigus
Research Fund. Preliminary reports of these findings were
presented at the Third Tricontinental Meeting of the Society for
Investigative Dermatology, the European Society for Dermatological
Research, and the Japanese Society for Investigative Dermatology,
Cologne, Germany, May 9, 1998, and at the 60th Annual Meeting of the
Society for Investigative Dermatology, Chicago, Illinois, May 7, 1999, and May 12, 2000, and published in abstract form in the
Journal of Investigative Dermatology 110:486,
1998, and Journal of Investigative Dermatology
112:250, 1999, respectively.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Dermatology,
University of California, Davis, UC Davis Medical Center, 4860 Y St.,
Suite 3400, Sacramento, CA 95817. Tel.: 916-734-6057; Fax:
916-734-6793; E-mail: sagrando@ucdavis.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W.-M. Heupel, P. Engerer, E. Schmidt, and J. Waschke Pemphigus Vulgaris IgG Cause Loss of Desmoglein-Mediated Adhesion and Keratinocyte Dissociation Independent of Epidermal Growth Factor Receptor Am. J. Pathol., February 1, 2009; 174(2): 475 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-M. Heupel, D. Zillikens, D. Drenckhahn, and J. Waschke Pemphigus Vulgaris IgG Directly Inhibit Desmoglein 3-Mediated Transinteraction J. Immunol., August 1, 2008; 181(3): 1825 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Stanley and M. Amagai Pemphigus, Bullous Impetigo, and the Staphylococcal Scalded-Skin Syndrome N. Engl. J. Med., October 26, 2006; 355(17): 1800 - 1810. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Roosterman, T. Goerge, S. W. Schneider, N. W. Bunnett, and M. Steinhoff Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev, October 1, 2006; 86(4): 1309 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Veldman, A. Pahl, S. Beissert, W. Hansen, J. Buer, D. Dieckmann, G. Schuler, and M. Hertl Inhibition of the transcription factor foxp3 converts desmoglein 3-specific type 1 regulatory T cells into th2-like cells. J. Immunol., March 1, 2006; 176(5): 3215 - 3222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Veldman, K. L. Gebhard, W. Uter, R. Wassmuth, J. Grotzinger, E. Schultz, and M. Hertl T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals J. Immunol., March 15, 2004; 172(6): 3883 - 3892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. T. Nguyen, J. Arredondo, A. I. Chernyavsky, Y. Kitajima, M. Pittelkow, and S. A. Grando Pemphigus Vulgaris IgG and Methylprednisolone Exhibit Reciprocal Effects on Keratinocytes J. Biol. Chem., January 16, 2004; 279(3): 2135 - 2146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tsunoda, T. Ota, M. Aoki, T. Yamada, T. Nagai, T. Nakagawa, S. Koyasu, T. Nishikawa, and M. Amagai Induction of Pemphigus Phenotype by a Mouse Monoclonal Antibody Against the Amino-Terminal Adhesive Interface of Desmoglein 3 J. Immunol., February 15, 2003; 170(4): 2170 - 2178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Scully and S. J. Challacombe PEMPHIGUS VULGARIS: UPDATE ON ETIOPATHOGENESIS, ORAL MANIFESTATIONS, AND MANAGEMENT Critical Reviews in Oral Biology & Medicine, September 1, 2002; 13(5): 397 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Caldelari, A. de Bruin, D. Baumann, M. M. Suter, C. Bierkamp, V. Balmer, and E. Muller A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris J. Cell Biol., May 14, 2001; 153(4): 823 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. T. Nguyen, A. Ndoye, K. D. Bassler, L. D. Shultz, M. C. Shields, B. S. Ruben, R. J. Webber, M. R. Pittelkow, P. J. Lynch, and S. A. Grando Classification, Clinical Manifestations, and Immunopathological Mechanisms of the Epithelial Variant of Paraneoplastic Autoimmune Multiorgan Syndrome: A Reappraisal of Paraneoplastic Pemphigus Arch Dermatol, February 1, 2001; 137(2): 193 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. T. Nguyen, A. Ndoye, and S. A. Grando Novel Human {alpha}9 Acetylcholine Receptor Regulating Keratinocyte Adhesion is Targeted by Pemphigus Vulgaris Autoimmunity Am. J. Pathol., October 1, 2000; 157(4): 1377 - 1391. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |