AI Article Synopsis
Article Abstract
Human serum albumin (HSA) is the most abundant protein in plasma and presents the particularity, with IgG, to have an extraordinary long serum half-life conferred by its interaction with the neonatal Fc receptor (FcRn). If the impact of IgG post-translational modifications (PTMs) on FcRn binding is well documented, it is far less reported for HSA despite numerous PTMs occurring on the protein in plasma. HSA is susceptible to numerous degradation reactions in plasma, because of aging, oxidative stress or liver and pancreas related pathologies. In the present study, we combined FcRn affinity chromatography and mass spectrometry to investigate the impact of HSA PTMs upon FcRn binding. This methodology presents the advantage to distinguish the effect of a single modification from a plasma HSA preparation made of a mixture of different isoforms. Cys oxidation, Lys glycation, and Leu C-terminal truncation, which are modifications related to several pathological conditions, were demonstrated to act negatively on HSA-FcRn interaction. The HSA-FcRn binding alteration generated by these modifications is consistent with their vicinity with the interaction interface of the two proteins. Results were discussed regarding altered half-life of HSA observed in several disease states and pave the way toward new understandings of the hypoalbuminemia pathogenesis. SIGNIFICANCE STATEMENT: In this study, we investigated the impact of several post-translational modifications of HSA toward its ability to bind to the neonatal Fc receptor using in vitro affinity chromatography, mass spectrometry, and surface plasmon resonance. Cys34 oxidation, Lys525 glycation, and Leu585 C-terminal truncation were demonstrated to decrease HSA-FcRn binding. These modifications occurring in circulating HSA were discussed in relation to several pathologies as well as for the use of HSA as a therapeutic protein.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798133 | PMC |
| http://dx.doi.org/10.1002/pro.3733 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pediatric high-grade gliomas (pHGG) and pediatric diffuse midline gliomas (pDMG) are devastating diseases without durable and curative options. Although targeted immunotherapy has shown promise, the field lacks immunocompetent animal models to study these processes in detail. To achieve this, we developed a fully immunocompetent, genetically engineered mouse model (GEMM) for pDMG and pHGG that incorporates the glioma-associated antigen, interleukin 13 receptor alpha 2 (IL13RA2).
View Article and Find Full Text PDFClinical efficacy of efgartigimod combined with intravenous methylprednisolone in the acute phase of neuromyelitis optica spectrum disorders.
Orphanet J Rare Dis
December 2024
Department of Neurology, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
Background: Neuromyelitis Optica Spectrum Disorders (NMOSD) comprise a group of autoimmune-mediated, inflammatory, demyelinating central nervous system diseases caused by aquaporin-4 (AQP4) IgG autoantibodies. Efgartigimod is a human IgG Fc fragment that reduces antibody titers by targeting the neonatal Fc receptor (FcRn). This study documents the efficacy of efgartigimod combined with intravenous methylprednisolone (IVMP) in the acute phase of NMOSD.
View Article and Find Full Text PDFEvaluation of the effect of rozanolixizumab on pregnancy outcomes and pre- and postnatal development in cynomolgus monkeys.
Reprod Toxicol
December 2024
Labcorp, Münster, Germany.
Rozanolixizumab, a humanised immunoglobulin (Ig) G4 monoclonal antibody that selectively inhibits binding of IgG to the neonatal Fc receptor (FcRn), was evaluated in an embryo-foetal enhanced pre- and postnatal development (ePPND) study. Pregnant female cynomolgus monkeys (19 per group) received subcutaneous rozanolixizumab 50mg/kg or 150mg/kg or vehicle every 3 days from gestation day 20 until delivery. The proportion of pregnancy losses was 15.
View Article and Find Full Text PDFAdvances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders.
Semin Respir Crit Care Med
December 2024
Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio.
Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications.
View Article and Find Full Text PDFBest practices in the laboratory diagnosis, prognostication, prediction, and monitoring of Graves' disease: role of TRAbs.
BMC Endocr Disord
December 2024
Department of Endocrinology, Osmania Medical College & Osmania General Hospital, Hyderabad, Telangana, India.
Article Synopsis
- Graves' disease (GD) is an autoimmune disorder where the body's antibodies stimulate the TSH receptor, causing excessive thyroid hormone production.
- Diagnosis typically involves assessing symptoms and a thyroid panel, with specific tests for TSH Receptor Antibodies (TRAbs) aiding in diagnosis and management strategies.
- Recent guidelines from experienced endocrinologists emphasize the importance of TRAbs in GD management to improve effectiveness and decision-making for healthcare providers, particularly in South Asia.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!