Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from pemphigoid gestationis patients.
Eur J Immunol
; 36(4): 1039-48, 2006 Apr.
Article
in En
| MEDLINE
| ID: mdl-16552711
ABSTRACT
Pemphigoid gestationis (PG) is a subepidermal autoimmune blistering disease characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16th non-collagenous domain A (NC16A) of type XVII collagen. The aim of the present study was to map the pathogenically relevant epitopes targeted by blister-inducing patients' autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leukocyte-dependent dermal-epidermal separation. Pre-adsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients. Using overlapping synthetic peptides, we demonstrated that PG autoantibodies bind to two defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Importantly, pre-adsorption using an affinity matrix containing these epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies. This study identifies the epitopes relevant for blister induction in PG and should facilitate the development of an antigen-specific immunoadsorption therapy for this disease.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoantibodies
/
Pemphigoid Gestationis
/
Dermis
/
Collagen Type XVIII
/
Epidermis
/
Epitopes
Limits:
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Eur J Immunol
Year:
2006
Document type:
Article
Affiliation country: