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Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display.
- Source :
-
Journal of Clinical Investigation . Apr2005, Vol. 115 Issue 4, p888-899. 12p. 3 Color Photographs, 2 Black and White Photographs, 1 Diagram, 2 Charts, 3 Graphs. - Publication Year :
- 2005
-
Abstract
- Pemphigus is a life-threatening blistering disorder of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein 3 (Dsg3) and Dsg1. Mechanisms of antibody pathogenicity are difficult to characterize using polyclonal patient sera. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fragments (scFvs) from a patient with active mucocutaneous pemphigus vulgaris. ScFv mAbs demonstrated binding to Dsg3 or Dsg1 alone, or both Dsg3 and Dsg1. Inhibition ELISA showed that the epitopes defined by these scFvs are blocked by autoantibodies from multiple pemphigus patients. Injection of scFvs into neonatal mice identified 2 pathogenic scFvs that caused blisters histologically similar to those observed in pemphigus patients. Similarly, these 2 scFvs, but not others, induced cell sheet dissociation of cultured human keratinocytes, indicating that both pathogenic and nonpathogenic antibodies were isolated. Genetic analysis of these mAbs showed restricted patterns of heavy and light chain gene usage, which were distinct for scFvs with different desmoglein-binding specificities. Detailed characterization of these pemphigus mAbs should lead to a better understanding of the immunopathogenesis of disease and to more specifically targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SKIN diseases
*MONOCLONAL antibodies
*DERMATOLOGY
*SERUM
*GENETICS
*IMMUNOGLOBULINS
*AMINO acids
*ANIMAL experimentation
*ANIMAL populations
*ANTIGENS
*AUTOANTIBODIES
*CELL culture
*COMPARATIVE studies
*DOCUMENTATION
*EPIDERMIS
*GENETIC techniques
*GLYCOPROTEINS
*IMMUNOLOGICAL adjuvants
*IMMUNOLOGY technique
*KERATINOCYTES
*RESEARCH methodology
*MEDICAL cooperation
*MICE
*PEMPHIGUS
*PEPTIDES
*RESEARCH
*RESEARCH funding
*STATISTICAL sampling
*EVALUATION research
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 115
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 16624339
- Full Text :
- https://doi.org/10.1172/JCI200524185