FcRn mediates elongated serum half-life of human IgG in cattle

I. Kacskovics, Zsuzsanna Kis, B. Mayer, Anthony P. West, Noreen E. Tiangco, Mulualem Tilahun, L. Cervenák, Pamela J. Bjorkman, Richard A. Goldsby, O. Szenci, Lennart Hammarström

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

IgG has the longest survival time in the circulation of the Ig classes and the lowest fractional catabolic rate. The neonatal Fc receptor (FcRn) plays an important role in regulating these processes. Recently, we have cloned the bovine neonatal Fc receptor (bFcRn) alpha chain and detected its expression in various epithelial cells which are mediating IgG secretion. However, its function in IgG homeostasis has not been investigated. In the current study, we analyzed the binding affinity of bovine and human IgGs to bFcRn using surface plasmon resonance and by in vitro radioreceptor binding assays. As human IgG binds stronger to the bFcRn, than bovine IgG at pH 6, we subsequently analyzed its catabolism in normal and transchromosomic calves that produce human Igs. Pharmacokinetic studies showed that human IgG had ∼33 days serum half-life both in normal and transchromosomic calves, which is more than two times longer than its bovine counterpart. We also demonstrate FcRn expression in endothelial cells and in the kidney which are supposed to be involved in IgG metabolism. These data suggest that bFcRn is involved in IgG homeostasis in cattle and furthermore, that the transchromosomic calves producing human Igs can effectively protect their human IgGs which have implications for successful large-scale production of therapeutic antibodies.

Original languageEnglish
Pages (from-to)525-536
Number of pages12
JournalInternational Immunology
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Half-Life
Immunoglobulin G
Serum
Homeostasis
Radioligand Assay
Surface Plasmon Resonance
Antibody Formation
Endothelial Cells
Pharmacokinetics
Epithelial Cells
Kidney
Survival

Keywords

  • Antibody
  • Clearance
  • Interaction
  • Therapeutic antibodies
  • Transchromosomic catte

ASJC Scopus subject areas

  • Immunology

Cite this

Kacskovics, I., Kis, Z., Mayer, B., West, A. P., Tiangco, N. E., Tilahun, M., ... Hammarström, L. (2006). FcRn mediates elongated serum half-life of human IgG in cattle. International Immunology, 18(4), 525-536. https://doi.org/10.1093/intimm/dxh393

FcRn mediates elongated serum half-life of human IgG in cattle. / Kacskovics, I.; Kis, Zsuzsanna; Mayer, B.; West, Anthony P.; Tiangco, Noreen E.; Tilahun, Mulualem; Cervenák, L.; Bjorkman, Pamela J.; Goldsby, Richard A.; Szenci, O.; Hammarström, Lennart.

In: International Immunology, Vol. 18, No. 4, 04.2006, p. 525-536.

Research output: Contribution to journalArticle

Kacskovics, I, Kis, Z, Mayer, B, West, AP, Tiangco, NE, Tilahun, M, Cervenák, L, Bjorkman, PJ, Goldsby, RA, Szenci, O & Hammarström, L 2006, 'FcRn mediates elongated serum half-life of human IgG in cattle', International Immunology, vol. 18, no. 4, pp. 525-536. https://doi.org/10.1093/intimm/dxh393
Kacskovics, I. ; Kis, Zsuzsanna ; Mayer, B. ; West, Anthony P. ; Tiangco, Noreen E. ; Tilahun, Mulualem ; Cervenák, L. ; Bjorkman, Pamela J. ; Goldsby, Richard A. ; Szenci, O. ; Hammarström, Lennart. / FcRn mediates elongated serum half-life of human IgG in cattle. In: International Immunology. 2006 ; Vol. 18, No. 4. pp. 525-536.
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