Immunoadsorber for specific apheresis of autoantibodies in the treatment of bullous pemphigoid.
Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies against two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. As the pathogenic relevance of antibodies against the immunodominant NC16A domain of BP180 has been clearly demonstrated, specific removal of these antibodies should be a rational therapeutic approach. Here, we evaluated three recombinant forms of bacterially produced BP180 NC16A, a monomer, trimer, and tetramer, together with different matrices for their efficacy to specifically adsorb autoantibodies from BP plasma samples. An adsorber consisting of NC16A-trimer coupled to NHS-activated Sepharose 4 Fast Flow revealed satisfying adsorption rates and a high specificity. The NC16A-trimer adsorber was regenerable and autoclavable. It has the potential to be used for specific immunoadsorption to treat severe and refractory BP and other pemphigoid diseases associated with BP180 NC16A reactivity.
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany. m.mersmann@euroimmun.de.
Michael
M
Mersmann
Lübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Jenny
J
Dworschak
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany.
Kristin
K
Ebermann
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany.
Lars
L
Komorowski
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany.
Wolfgang
W
Schlumberger
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany.
Winfried
W
Stöcker
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Detlef
D
Zillikens
Institute of Experimental Immunology, Euroimmun AG, Seekamp 31, 23560, Lübeck, Germany.
Christian
C
Probst
Lübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.|Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Enno
E
Schmidt
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001781:Blood Component Removal / Q000295:instrumentation* / Q000379:methods*; D002352:Carrier Proteins / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D000071821:Dystonin; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D017434:Protein Structure, Tertiary; D012685:Sepharose / Q000378:metabolism; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012685:Sepharose; D000097805:Collagen Type XVII; C486268:DST protein, human
Autoantibodies; BP180; Bullous pemphigoid; Immunoadsorption