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Specific immunoadsorption of pathogenic autoantibodies in pemphigus requires the entire ectodomains of desmogleins
Author(s) -
Langenhan Jana,
Dworschak Jenny,
Saschenbrecker Sandra,
Komorowski Lars,
Schlumberger Wolfgang,
Stöcker Winfried,
Westermann Jürgen,
Recke Andreas,
Zillikens Detlef,
Schmidt Enno,
Probst Christian
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12355
Subject(s) - pemphigus foliaceus , immunoadsorption , desmoglein , pemphigus , pemphigus vulgaris , acantholysis , autoantibody , antibody , epitope mapping , epitope , desmoglein 3 , immunology , biology
Pemphigus foliaceus ( PF ) and pemphigus vulgaris ( PV ) are life‐threatening autoimmune blistering skin diseases. They are characterized by circulating autoantibodies which bind to the ectodomains of desmoglein (Dsg) 1 and D sg3. These antibodies induce acantholysis in skin and mucous membranes. In severe cases of pemphigus, immunoadsorption is applied to remove total IgG from patient plasma using protein A or other ligands. To develop a specific adsorber for anti‐Dsg antibodies, epitope mapping studies of D sg1 and D sg3 ectodomains were conducted. Dsg variants were expressed on the surface of HEK ‐293 cells and analysed for reactivity with pemphigus and control sera by indirect immunofluorescence technique. For Dsg1, a construct consisting of domain 1 directly fused to domain 5, seemed to be suitable for specific immunoadsorption of anti‐Dsg1 antibodies. The recognized epitopes were mainly conformation‐dependent. However, adsorption of pemphigus foliaceus IgG using this protein coupled to a Sepharose matrix did not completely remove pathogenicity from the sera, as proven by a keratinocyte dissociation assay. In contrast, full‐length Dsg1 and Dsg3 ectodomains were able to specifically adsorb anti‐Dsg antibodies and to efficiently eliminate pathogenicity. Therefore, the complete and correctly folded ectodomains of both desmogleins are required for therapeutic immunoadsorption.