In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc receptor.
Sci Rep
; 8(1): 5141, 2018 03 23.
Article
em En
| MEDLINE
| ID: mdl-29572538
ABSTRACT
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 (ZFcRn) 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 ZFcRn and ZFcRn-ABD were found to result in an up to 40% reduction of the IgG serum-level after 5 days. Potential applications of ZFcRn as a general treatment modality for autoimmune diseases are discussed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Proteínas Recombinantes de Fusão
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Imunoglobulina G
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Receptores Fc
/
Antígenos de Histocompatibilidade Classe I
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article