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 effec...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.892534/full |
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| author | E. Sally Ward Deborah Gelinas Erwin Dreesen Jolien Van Santbergen Jan Terje Andersen Jan Terje Andersen Nicholas J. Silvestri Joseph E. Kiss Darrell Sleep Daniel J. Rader John J. P. Kastelein Els Louagie Gestur Vidarsson Gestur Vidarsson Isabel Spriet Isabel Spriet |
| author_facet | E. Sally Ward Deborah Gelinas Erwin Dreesen Jolien Van Santbergen Jan Terje Andersen Jan Terje Andersen Nicholas J. Silvestri Joseph E. Kiss Darrell Sleep Daniel J. Rader John J. P. Kastelein Els Louagie Gestur Vidarsson Gestur Vidarsson Isabel Spriet Isabel Spriet |
| author_sort | E. Sally Ward |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T04:20:51Z |
| format | Article |
| id | doaj.art-184d31362c494626a9242fddebe1de64 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T04:20:51Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-184d31362c494626a9242fddebe1de642022-12-22T00:38:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.892534892534Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune DisordersE. Sally Ward0Deborah Gelinas1Erwin Dreesen2Jolien Van Santbergen3Jan Terje Andersen4Jan Terje Andersen5Nicholas J. Silvestri6Joseph E. Kiss7Darrell Sleep8Daniel J. Rader9John J. P. Kastelein10Els Louagie11Gestur Vidarsson12Gestur Vidarsson13Isabel Spriet14Isabel Spriet15Cancer Sciences Unit, Centre for Cancer Immunology, University of Southampton, Southampton, United KingdomMedical Affairs, argenx, Boston, MA, United StatesDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, BelgiumDiscovery, argenx, Ghent, BelgiumDepartment of Immunology, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Pharmacology, University of Oslo, Oslo, NorwayDepartment of Neurology, University at Buffalo, Buffalo, NY, United StatesVitalant Northeast Division and Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesFreelance Consultant, Nottingham, United Kingdom0Departments of Genetics and Medicine, Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States1Department of Vascular Medicine, Genetics of Cardiovascular Disease, Academic Medical Center (AMC) of the University of Amsterdam, Amsterdam, NetherlandsDiscovery, argenx, Ghent, Belgium2Department of Experimental Immunohematology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands3Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands4Department of Clinical Pharmacology and Pharmacotherapy, KU Leuven, Leuven, Belgium5Pharmacy Department, University Hospitals Leuven, Leuven, BelgiumSerum 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.892534/fullalbuminautoimmuneFcRnhypoalbuminemiaIgGmonoclonal antibody |
| spellingShingle | E. Sally Ward Deborah Gelinas Erwin Dreesen Jolien Van Santbergen Jan Terje Andersen Jan Terje Andersen Nicholas J. Silvestri Joseph E. Kiss Darrell Sleep Daniel J. Rader John J. P. Kastelein Els Louagie Gestur Vidarsson Gestur Vidarsson Isabel Spriet Isabel Spriet Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders Frontiers in Immunology albumin autoimmune FcRn hypoalbuminemia IgG monoclonal antibody |
| title | Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders |
| title_full | Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders |
| title_fullStr | Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders |
| title_full_unstemmed | Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders |
| title_short | Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders |
| title_sort | clinical significance of serum albumin and implications of fcrn inhibitor treatment in igg mediated autoimmune disorders |
| topic | albumin autoimmune FcRn hypoalbuminemia IgG monoclonal antibody |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.892534/full |
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