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In vivo depletion o...
In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc receptor
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- Seijsing, Johan (författare)
- KTH,Skolan för bioteknologi (BIO),Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
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- Yu, Shengze (författare)
- KTH,Skolan för bioteknologi (BIO)
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- Frejd, Fredrik Y. (författare)
- Affibody AB, Gunnar Asplunds Alle 24, S-17163 Solna, Sweden.
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- Hoiden-Guthenberg, Ingmarie (författare)
- Affibody AB, Gunnar Asplunds Alle 24, S-17163 Solna, Sweden.
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- Gräslund, Torbjörn (författare)
- KTH,Skolan för bioteknologi (BIO)
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(creator_code:org_t)
- 2018-03-23
- 2018
- Engelska.
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Lowering the total level of Immunoglobulin G (IgG) in circulation is a promising general treatment option for many autoimmune diseases driven by pathogenic autoantibodies. The half-life of IgG in circulation is unusually long as a consequence of its interaction with the neonatal Fc receptor (FcRn), which protects it from lysosomal degradation by cells in contact with blood. Blocking the IgG/FcRn interaction prevents FcRn-mediated rescue, which may lead to increased catabolism and a lowering of the total IgG level. Here, we find that an engineered alternative scaffold protein, an affibody molecule, interacting specifically with FcRn, is able to block the IgG/FcRn interaction in vitro. The affibody molecule (Z(FcRn)) was expressed alone or as a fusion to an albumin binding domain (ABD), to extend its half-life in circulation, in both cases with retained affinity and blocking potential. Repeated i.v. injections in mice of Z(FcRn) and Z(FcRn)-ABD were found to result in an up to 40% reduction of the IgG serum-level after 5 days. Potential applications of Z(FcRn) as a general treatment modality for autoimmune diseases are discussed.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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