Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from pemphigoid gestationis patients.
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.
Herrero-González
Josep E
JE
Department of Dermatology, University of Lübeck, Lübeck, Germany.
Brauns
Olaf
O
Egner
Ralf
R
Rönspeck
Wolfgang
W
Mascaró
José M
JM
Jonkman
Marcel F
MF
Zillikens
Detlef
D
Sitaru
Cassian
C
D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D043170:Collagen Type XVIII / Q000235:genetics / Q000276:immunology*; D020405:Dermis / Q000276:immunology / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000276:immunology / Q000473:pathology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007163:Immunosorbent Techniques; D066298:In Vitro Techniques; D006559:Pemphigoid Gestationis / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy
D001323:Autoantibodies; D043170:Collagen Type XVIII; D000939:Epitopes