Isotypes and Antigenic Profiles of Pemphigus Foliaceus and Pemphigus Vulgaris Autoantibodies
Autor: | Mary K. Hacker, Mong-Shang Lin, Janet A. Fairley, Marleen M. Janson |
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Rok vydání: | 2002 |
Předmět: |
Immunoblotting
Immunology Enzyme-Linked Immunosorbent Assay Biology Desmoglein Epitope Epitopes Mice medicine Animals Humans Immunology and Allergy Fluorescent Antibody Technique Indirect Pemphigus foliaceus Autoantibodies Skin Mice Inbred BALB C Mucous Membrane Desmoglein 3 integumentary system Linear epitope Desmoglein 1 Pemphigus vulgaris Haplorhini Cadherins medicine.disease Isotype Recombinant Proteins Immunoglobulin Isotypes Pemphigus Immunoglobulin G Conformational epitope |
Zdroj: | Clinical Immunology. 105:64-74 |
ISSN: | 1521-6616 |
DOI: | 10.1006/clim.2002.5259 |
Popis: | In this study we systematically characterized isotype profiles and antigenic and tissue specificity of antidesmoglein autoantibodies from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) using enzyme-linked immunoabsorbent assays (ELISA), indirect immunofluorescence (IIF) staining, and immunoblotting (IB). In PF, we found that IgG1 antidesmoglein-1 (Dsg1) reacts with a linear epitope(s) on the ectodomain of Dsg1, while its IgG4 counterpart recognizes a conformational epitope(s). These two subclasses of anti-Dsg1 are both capable of recognizing tissues from monkey esophagus and adult human skin, but IgG1 is not able to react with mouse skin, which may explain why this isotype of anti-Dsg1 failed to induce PF-like lesions in the passive transfer animal model. In mucosal PV patients, we found that both IgG1 and IgG4 only recognized monkey esophagus tissue by IIF, except in one patient, indicating that these antibodies react with a unique conformational epitope(s) that is present in mucosal but not skin tissue. In generalized PV, IgG1 anti-Dsg3 autoantibodies appeared to recognize a linear epitope(s) on the Dsg3 ectodomain. In contrast, IgG4 anti-Dsg3 antibodies recognized both linear and conformational epitopes on the Dsg3 molecule. Interestingly, the IgG1 anti-Dsg3 antibodies failed to react with human and mouse skin tissues, suggesting that this subclass of autoantibodies may not play an essential role in the development of PV suprabasilar lesions. In summary, we conclude that this study further elucidates the pathological mechanisms of PF and PV autoantibodies by revealing their distinct isotype and antigenic profiles. This information may help us to better understand the autoimmune mechanisms underlying the development of pemphigus. |
Databáze: | OpenAIRE |
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