In:
Experimental Dermatology, Wiley, Vol. 23, No. 4 ( 2014-04), p. 253-259
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0906-6705
,
1600-0625
DOI:
10.1111/exd.2014.23.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2026228-0
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