Targeting pemphigus autoantibodies through their heavy-chain variable region genes.

Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Research Abstract Details 

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Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Abstract Text:

Aimee S Payne,Don L Siegel,John R Stanley,

Pemphigus vulgaris (PV) is a potentially fatal blistering disease characterized by autoantibodies against cell surface adhesion proteins desmoglein (Dsg) 3 and Dsg1. Previous studies using phage display to clone Dsg-reactive monoclonal antibodies from a PV patient demonstrated that a limited number of antibody variable region genes encode the autoantibody repertoire, with different genes for pathogenic and non-pathogenic mAbs. Here, we investigated the feasibility of specific autoantibody targeting in pemphigus. We produced rabbit anti-idiotypic antibodies against two pathogenic and two non-pathogenic PV mAbs. Antisera inhibited binding of the immunizing mAb to Dsgs by ELISA as well as pathogenicity against cultured human keratinocytes. Antisera also inhibited other mAbs using the same variable region heavy chain (V(H)) genes, despite different light chains or somatic mutations. Additionally, peptide phage display identified peptide sequences that bound PV mAbs in a V(H)-specific manner. To evaluate the therapeutic potential of V(H) gene-targeted reagents, preimmune sera and antisera were used to adsorb pathogenic antibodies from PV sera. Pooled antisera significantly reduced pathogenic activity from the original PV patient's serum and bound pathogenic antibodies from two other PV sera, suggesting shared autoantibody V(H) gene usage among PV patients. Together, these data suggest novel V(H) gene-targeted approaches toward PV treatment.

Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Publishing Authors By Initials

AS Payne,DL Siegel,JR Stanley,

For similar skin and connective tissue diseases: skin diseases: skin diseases, vesiculobullous: pemphigus research abstracts see: skin and connective tissue diseases: skin diseases: skin diseases, vesiculobullous: pemphigus research

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Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of investigative dermatology

VOLUME: 127

Page Numbers: 1681-91

Journal Abbreviation: J. Invest. Dermatol.

ISSN: 1523-1747

DAY: 29

MONTH: 03

YEAR: 2007

Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Information

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LANGUAGE: eng

NlmUniqueID: 426720

Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Keywords Mesh Terms:

KEYWORDS: Pemphigus

MESH TERMS: therapy

Chemical & Substance for Abstract: Targeting pemphigus autoantibodies through their heavy-chain variable region genes. Information

Substance Name: Immunoglobulin Variable Region

Registry Number: 0

Grant and Affiliation Information for Targeting pemphigus autoantibodies through their heavy-chain variable region genes.

AFFILIATION: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. paynea@mail.med.upenn.edu

Country: United States

AGENCY: United States NIAMS

GRANT: T32-AR07465

ACRONYM: AR

MEDLINETA: J Invest Dermatol

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