Introduction: The glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation.
Purpose: In this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.
Methods: Mice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies.
Results: Using a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells.
Conclusion: The study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.
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http://dx.doi.org/10.3389/fendo.2023.1243942 | DOI Listing |
Anal Chem
January 2025
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan.
Prior to mass spectrometry (MS) analysis, pretreatment of low-abundance glycopeptides is vital for identifying protein glycosylation. In this study, we fabricated an environmentally friendly citric-acid-modified cellulose monolith (CCM) characterized by a coral-like porous structure and high-density hydrophilic groups using a thermally induced phase separation (TIPS) method. The CCM production leverages biomass resources, specifically cellulose and citric acid, utilizing TIPS to synthesize continuous porous materials through a straightforward heating and cooling process of polymer solutions.
View Article and Find Full Text PDFOrg Biomol Chem
January 2025
School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China.
Glycosite-specific antibody-drug conjugates (gsADCs), which carry cytotoxic payloads at the conserved -glycosylation site, N297, of an IgG, have emerged as a promising ADC format with better therapeutic index. Conjugating the payloads aldehyde-based chemistry is more friendly to IgGs, and has been widely investigated. However, the efficiency of introducing an aldehyde tag at the N297 site is poor due to the complicated procedures required, such as the multiple-enzyme-catalyzed IgG glycoengineering process and the successive oxidation step, which always results in heterogeneous products and poor stability.
View Article and Find Full Text PDFNat Commun
January 2025
Centre for translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation).
View Article and Find Full Text PDFAnal Methods
January 2025
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34450, Turkey.
Sci Rep
December 2024
Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), Albinusdreef 2, 2333ZA, Leiden, Zuid-Holland, The Netherlands.
Antibody glycosylation patterns can affect antibody functionality and thereby contribute to protection against invading pathogens. During pregnancy, maternal antibodies can be transferred through the placenta and contribute to modulating both the mother's and her child's immune responses. Although several studies of IgG glycosylation during pregnancy have been carried out, very few cohorts studied were from sub-Saharan Africa, where exposure to microorganisms and parasites is high.
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