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In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc receptor
KTH, School of Biotechnology (BIO). Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden..
KTH, School of Biotechnology (BIO).
Affibody AB, Gunnar Asplunds Alle 24, S-17163 Solna, Sweden..
Affibody AB, Gunnar Asplunds Alle 24, S-17163 Solna, Sweden..
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5141Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 5141
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Biological Sciences
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URN: urn:nbn:se:kth:diva-225708DOI: 10.1038/s41598-018-23481-5ISI: 000428163600012PubMedID: 29572538Scopus ID: 2-s2.0-85044363795OAI: oai:DiVA.org:kth-225708DiVA, id: diva2:1196749
Note

QC 20180411

Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved

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Gräslund, Torbjörn

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