Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause

IntroductionThe 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...

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Main Authors: Priti Gupta, Tibor Sághy, Jauquline Nordqvist, Jonas Nilsson, Hans Carlsten, Karin Horkeby, Petra Henning, Cecilia Engdahl
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1243942/full
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author Priti Gupta
Priti Gupta
Priti Gupta
Tibor Sághy
Tibor Sághy
Tibor Sághy
Jauquline Nordqvist
Jonas Nilsson
Hans Carlsten
Karin Horkeby
Petra Henning
Cecilia Engdahl
Cecilia Engdahl
Cecilia Engdahl
author_facet Priti Gupta
Priti Gupta
Priti Gupta
Tibor Sághy
Tibor Sághy
Tibor Sághy
Jauquline Nordqvist
Jonas Nilsson
Hans Carlsten
Karin Horkeby
Petra Henning
Cecilia Engdahl
Cecilia Engdahl
Cecilia Engdahl
author_sort Priti Gupta
collection DOAJ
description IntroductionThe 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.PurposeIn this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.MethodsMice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies.ResultsUsing 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.ConclusionThe 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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spelling doaj.art-b8bbd8637e8847ecb2557e974349e13d2023-09-11T11:27:03ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-09-011410.3389/fendo.2023.12439421243942Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopausePriti Gupta0Priti Gupta1Priti Gupta2Tibor Sághy3Tibor Sághy4Tibor Sághy5Jauquline Nordqvist6Jonas Nilsson7Hans Carlsten8Karin Horkeby9Petra Henning10Cecilia Engdahl11Cecilia Engdahl12Cecilia Engdahl13Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenSciLifeLab, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenSciLifeLab, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenProteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenSciLifeLab, University of Gothenburg, Gothenburg, SwedenIntroductionThe 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.PurposeIn this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.MethodsMice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies.ResultsUsing 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1243942/fullIgGestrogenIgG-glycosylationsialylationsialic acidanimal
spellingShingle Priti Gupta
Priti Gupta
Priti Gupta
Tibor Sághy
Tibor Sághy
Tibor Sághy
Jauquline Nordqvist
Jonas Nilsson
Hans Carlsten
Karin Horkeby
Petra Henning
Cecilia Engdahl
Cecilia Engdahl
Cecilia Engdahl
Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
Frontiers in Endocrinology
IgG
estrogen
IgG-glycosylation
sialylation
sialic acid
animal
title Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
title_full Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
title_fullStr Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
title_full_unstemmed Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
title_short Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
title_sort impact of estrogen on igg glycosylation and serum protein glycosylation in a murine model of healthy postmenopause
topic IgG
estrogen
IgG-glycosylation
sialylation
sialic acid
animal
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1243942/full
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