Pathogenic human monoclonal antibody against desmoglein 3
| Autor: | Mukesh Kumar, Kailash C. Bhol, Mong-Shang Lin, Lisa A. Cavacini, Shih-Wei Yeh, Mark Duval, Marshall R. Posner, A. Razzaque Ahmed |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Keratinocytes
medicine.drug_class Blotting Western Immunology Biology Monoclonal antibody Mice medicine Animals Humans Immunology and Allergy Fluorescent Antibody Technique Indirect education Mice Inbred BALB C education.field_of_study Desmoglein 3 integumentary system Acantholysis Pemphigus vulgaris Autoantibody Antibodies Monoclonal Intradermal Tests medicine.disease Immunohistochemistry medicine.anatomical_structure Animals Newborn Desmoglein 1 Immunoglobulin G biology.protein Immunotherapy Antibody Keratinocyte Epitope Mapping Pemphigus |
| Zdroj: | Clinical Immunology. 120:68-75 |
| ISSN: | 1521-6616 |
| Popis: | Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous disease associated with production of IgG autoantibodies to desmoglein 3 (Dsg3), a 130-kDa epidermal cadherin protein. The binding of pathogenic antibody to Dsg3 on epidermal keratinocytes leads to loss of intercellular adhesion and results in intraepithelial blister formation. Here, we describe a human monoclonal antibody, PVMAB786, a Dsg3-specific IgG4 antibody, from an untreated patient with active PV. The antibody reacts with a 130-kDa protein on keratinocyte cell surfaces and recombinant Dsg3 protein, but not desmoglein 1 protein. PVMAB786 induces acantholysis in normal human skin and mucous membranes and induces a clinical and histological profile similar to human PV when injected into neonatal mice. PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V gene and isotype usage in PV pathogenesis. |
| Databáze: | OpenAIRE |
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