Document Detail

IgG autoantibodies from bullous pemphigoid (BP) patients bind antigenic sites on both the extracellular and the intracellular domains of the BP antigen 180.
MedLine Citation:
PMID:  9989787     Owner:  NLM     Status:  MEDLINE    
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 NH2-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 ofBP180 harbors functionally important regions, it is possible that autoantibodies against the ICD of BP180 have pathogenic significance for the progression of the disease.
J Perriard; F Jaunin; B Favre; L Büdinger; M Hertl; J H Saurat; L Borradori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  112     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-23     Completed Date:  1999-02-23     Revised Date:  2013-01-18    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  141-7     Citation Subset:  IM    
Department of Dermatology, DHURDV, University Hospital of Geneva, Switzerland.
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MeSH Terms
Aged, 80 and over
Antibodies, Anti-Idiotypic / blood,  metabolism
Autoantibodies / blood,  metabolism
Autoantigens / immunology*
COS Cells
Extracellular Space / immunology
Immunodominant Epitopes / metabolism*
Intracellular Membranes / immunology
Middle Aged
Non-Fibrillar Collagens
Pemphigoid, Bullous / blood,  immunology*,  physiopathology
Recombinant Proteins / analysis,  immunology
Reg. No./Substance:
0/Antibodies, Anti-Idiotypic; 0/Autoantibodies; 0/Autoantigens; 0/Immunodominant Epitopes; 0/Non-Fibrillar Collagens; 0/Recombinant Proteins; 0/anti-IgE antibodies; 0/collagen type XVII

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