IgG Autoantibodies from Bullous Pemphigoid (BP) Patients Bind Antigenic Sites on Both the Extracellular and the Intracellular Domains of the BP Antigen 180
| Autor: | Michael Hertl, Luca Borradori, Lioba Büdinger, Jacqueline Perriard, Fabienne Jaunin, Jean-Hilaire Saurat, Bertrand Favre |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Immunoblotting Dermatology medicine.disease_cause Autoantigens Biochemistry Epitope law.invention Autoimmunity 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Antigen law Pemphigoid Bullous medicine Animals Humans hemidesmosome Molecular Biology Aged Autoantibodies 030304 developmental biology Aged 80 and over Autoimmune disease 0303 health sciences Immunodominant Epitopes business.industry Hemidesmosome autoimmunity Autoantibody Intracellular Membranes Cell Biology Middle Aged Non-Fibrillar Collagens medicine.disease Virology Molecular biology Recombinant Proteins Antibodies Anti-Idiotypic COS Cells Recombinant DNA Bullous pemphigoid Extracellular Space business |
| Zdroj: | Journal of Investigative Dermatology. 112:141-147 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.1999.00497.x |
| Popis: | Bullous pemphigoid (BP) and gestational pemphigoid (PG) are subepidermal blistering disorders associated with autoantibodies directed against two components of hemidesmosomes: the BP antigen 180 (BP180) and the BP antigen 230 (BP230). Autoantibodies against the extracellular domain (ECD) of BP180 are thought to play an initiatory role in subepidermal blister formation. To characterize the targeted antigenic sites on BP180, we have assessed the reactivity of sera from BP and PG patients against eukaryotic recombinant proteins encompassing various portions of the ECD and the intracellular domain (ICD) of BP180. Twenty-two of 22 (100%) BP sera that immunoblotted BP180 in keratinocyte extracts, bound a mutant form consisting of the entire ECD of BP180, whereas only three of these 22 sera (14%) reacted against the ECD of BP180 lacking the NC16A membrane proximal region. Thirteen out of the 22 (59%) BP sera recognized the ICD of BP180. Circulating IgG from a representative BP patient that was affinity purified against the ECD of BP180 did not bind the ICD when reblotted, indicating that there was no antigenic cross-reactivity between the ECD and the ICD of BP180. Reactivity against the ICD of BP180 was further ascertained by immunofluorescence microscopy studies showing that nine of the 22 (41%) BP sera stained COS-7 cells expressing the ICD of BP180. Using deletion mutants of the ICD of BP180, the majority of the sera was found to recognize the central region of the ICD of BP180. Specifically, an immunodominant region was localized to an 87-amino acid segment located towards the NH 2 -terminus of BP180. In contrast to BP sera, five of six (83%) PG sera contained IgG that recognized exclusively the NC16A region, whereas none bound to the ICD of BP180. Together, the results indicate that in BP, autoantibody reactivity to BP180 is not exclusively restricted to the NC16A region, but that additional antigenic determinants exist on the ICD of BP180. The observed heterogeneous immune response against BP180 might reflect intramolecular epitope spreading. Because the ICD of BP180 harbors functionally important regions, it is possible that autoantibodies against the ICD of BP180 have pathogenic significance for the progression of the disease. |
| Databáze: | OpenAIRE |
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