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Clinical significance of serum albumin and implications of FcRn inhibitor treatment in IgG-mediated autoimmune disorders

Clinical significance of serum albumin and implications of FcRn inhibitor treatment in IgG-mediated autoimmune disorders
Clinical significance of serum albumin and implications of FcRn inhibitor treatment in IgG-mediated autoimmune disorders
Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradation via a common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression.
albumin, autoimmune, FcRn, hypoalbuminemia, IgG, monoclonal antibody, serum protein
1664-3224
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Gelinas, Deborah
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Dreesen, Erwin
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Van Santbergen, Jolien
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Terje Andersen, Jan
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J. Silvestri, Nicholas
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E. Kiss, Joseph
c675c066-1126-4d69-8818-d21e89a10eeb
Sleep, Darrell
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J. Rader, Daniel
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J. P. Kastelein, John
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Louagie, Els
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Vidarsson, Gestur
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Spriet, Isabel
884ea2ea-883f-4bbd-afa0-2b1332d29f72
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Gelinas, Deborah
36f367d3-a991-4001-9864-5cd3be1714ca
Dreesen, Erwin
79e16c76-d9d0-4295-ace9-ee027992bd2c
Van Santbergen, Jolien
6cfe599f-4517-46db-bd95-1ada0a8970fa
Terje Andersen, Jan
3fbae877-de06-42fd-8449-20a708395da4
J. Silvestri, Nicholas
3c02bdbd-2411-45ad-ae69-334d70ee041c
E. Kiss, Joseph
c675c066-1126-4d69-8818-d21e89a10eeb
Sleep, Darrell
64525e0e-d6a8-45c4-83ad-96276a10c2a8
J. Rader, Daniel
8decf7f2-1b67-484a-9a26-ff3a7f800ede
J. P. Kastelein, John
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Louagie, Els
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Vidarsson, Gestur
119ead99-3a5f-4d67-b42c-a02606352cda
Spriet, Isabel
884ea2ea-883f-4bbd-afa0-2b1332d29f72

Ward, E. Sally, Gelinas, Deborah, Dreesen, Erwin, Van Santbergen, Jolien, Terje Andersen, Jan, J. Silvestri, Nicholas, E. Kiss, Joseph, Sleep, Darrell, J. Rader, Daniel, J. P. Kastelein, John, Louagie, Els, Vidarsson, Gestur and Spriet, Isabel (2022) Clinical significance of serum albumin and implications of FcRn inhibitor treatment in IgG-mediated autoimmune disorders. Frontiers in Immunology, 13 (JUN), [892534]. (doi:10.3389/fimmu.2022.892534).

Record type: Article

Abstract

Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradation via a common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression.

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fimmu-13-892534 - Version of Record
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In preparation date: 9 March 2022
Accepted/In Press date: 22 April 2022
Published date: 1 June 2022
Additional Information: Funding Information: DG, EL, and JVS are employees of argenx, the manufacturer of efgartigimod (FDA approved in gMG and under investigation in primary immune thrombocytopenia, pemphigus vulgaris and foliaceus, chronic inflammatory demyelinating polyneuropathy, bullous pemphigoid, and idiopathic inflammatory myopathy [myositis]). JTA has received funding from Syntimmune and argenx as part of fee-for-service agreements. ED is a postdoctoral research fellow of the Research Foundation – Flanders (grant number 12X9420N). JEK has participated on the Medical Advisory Committee of Sanofi Genzyme and Plasma Advisory Committee of Haemonetics. DR is the founder of Staten Biotechnology. NS is a member of the scientific advisory board and a speaker for argenx. IS, is supported by the Clinical Research Fund of the University Hospitals Leuven. ESW may receive royalties from patents owned by the UK Medical Research Council, UT Southwestern Medical Center, and Texas A&M University, and has financial interests in argenx, Astero BioPharma LLC, Astero Erado Inc., and Astero Technologies LLC. GV is a paid consultant for argenx. Funding Information: The authors thank Susan A. Leon, PhD, and Tam M. Nguyen-Cao, PhD, CMPP, of Claritas Scientific LLC for medical writing services; Ann D. Bledsoe Bollert, MA, CMPP, of Y-Axis Editorial for editorial services; Erwin Pannecoucke, PhD, of argenx for contributing to Figure 1 ; and Hans de Haard, PhD, of argenx for expert review of this manuscript. Publisher Copyright: Copyright © 2022 Ward, Gelinas, Dreesen, Van Santbergen, Andersen, Silvestri, Kiss, Sleep, Rader, Kastelein, Louagie, Vidarsson and Spriet.
Keywords: albumin, autoimmune, FcRn, hypoalbuminemia, IgG, monoclonal antibody, serum protein

Identifiers

Local EPrints ID: 467678
URI: http://eprints.soton.ac.uk/id/eprint/467678
ISSN: 1664-3224
PURE UUID: 73d1ba09-f6ee-4a46-9c75-7ee5038eea57
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 19 Jul 2022 16:39
Last modified: 17 Mar 2024 03:53

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Contributors

Author: E. Sally Ward ORCID iD
Author: Deborah Gelinas
Author: Erwin Dreesen
Author: Jolien Van Santbergen
Author: Jan Terje Andersen
Author: Nicholas J. Silvestri
Author: Joseph E. Kiss
Author: Darrell Sleep
Author: Daniel J. Rader
Author: John J. P. Kastelein
Author: Els Louagie
Author: Gestur Vidarsson
Author: Isabel Spriet

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