Immunoglobulin G glycome composition in transition from premenopause to postmenopause

Helena Deriš; Domagoj Kifer; Ana Cindrić; Tea Petrović; Ana Cvetko; Irena Trbojević-Akmačić; Ivana Kolčić; Ozren Polašek; Louise Newson; Tim Spector; Cristina Menni; Gordan Lauc

doi:10.1016/j.isci.2022.103897

Immunoglobulin G glycome composition in transition from premenopause to postmenopause

Helena Deriš, Domagoj Kifer, Ana Cindrić, Tea Petrović, Ana Cvetko, Irena Trbojević-Akmačić, Ivana Kolčić, Ozren Polašek, Louise Newson, Tim Spector, Cristina Menni, Gordan Lauc^*

^*Corresponding author for this work

Twin Research & Genetic Epidemiology

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

Gonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043–0.059, p < 0.001) and decrease in digalactosylated (−0.043/yr; 95%CI = −0.050 to −0.037, p < 0.001) and monosialylated glycans (−0.029/yr; 95%CI = −0.034 to −0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.

Original language	English
Article number	103897
Journal	iScience
Volume	25
Issue number	3
Early online date	10 Feb 2022
DOIs	https://doi.org/10.1016/j.isci.2022.103897
Publication status	Published - 18 Mar 2022

Keywords

Glycomics
Molecular biology
Reproductive medicine

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10.1016/j.isci.2022.103897Licence: CC BY

Cite this

@article{fa83d362f0014b91a244860de60c476d,

title = "Immunoglobulin G glycome composition in transition from premenopause to postmenopause",

abstract = "Gonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043–0.059, p < 0.001) and decrease in digalactosylated (−0.043/yr; 95%CI = −0.050 to −0.037, p < 0.001) and monosialylated glycans (−0.029/yr; 95%CI = −0.034 to −0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.",

keywords = "Glycomics, Molecular biology, Reproductive medicine",

author = "Helena Deri{\v s} and Domagoj Kifer and Ana Cindri{\'c} and Tea Petrovi{\'c} and Ana Cvetko and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Ivana Kol{\v c}i{\'c} and Ozren Pola{\v s}ek and Louise Newson and Tim Spector and Cristina Menni and Gordan Lauc",

note = "Funding Information: This study has been supported by the European Structural and Investment Funds IRI “CardioMetabolic” grant ( #KK.01.2.1.02.0321 ), Center of Competence in Molecular Diagnostics grant ( #KK.01.2.2.03.0006 ), and Croatian National Center of Research Excellence in Personalized Healthcare grant ( #KK.01.1.1.01.0010 ) and the Human Glycome Project. Equipment and products from Waters and New England Biolabs were used for this research. The Department of Twin Research receives support from grants from the Wellcome Trust ( 212904/Z/18/Z ) and the Medical Research Council (MRC)/ British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1 ), European Union , Chronic Disease Research Foundation (CDRF), Zoe Global Ltd., the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy{\textquoteright}|'s and St Thomas' NHS Foundation Trust in partnership with King{\textquoteright}|'s College London). C.M. is funded by the Chronic Disease Research Foundation and by the MRC AIM-HY project grant. Funding Information: This study has been supported by the European Structural and Investment Funds IRI ?CardioMetabolic? grant (#KK.01.2.1.02.0321), Center of Competence in Molecular Diagnostics grant (#KK.01.2.2.03.0006), and Croatian National Center of Research Excellence in Personalized Healthcare grant (#KK.01.1.1.01.0010) and the Human Glycome Project. Equipment and products from Waters and New England Biolabs were used for this research. The Department of Twin Research receives support from grants from the Wellcome Trust (212904/Z/18/Z) and the Medical Research Council (MRC)/British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1), European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd. the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy?|'s and St Thomas' NHS Foundation Trust in partnership with King?|'s College London). C.M. is funded by the Chronic Disease Research Foundation and by the MRC AIM-HY project grant. D.K.: Data analysis and interpretation, Visualization, Writing?Original draft preparation, Writing?Review and editing; H.D.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; A.Ci.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; T.P.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; A.Cv.: Quantification of IgG N-glycans, Data interpretation, Writing?Original draft preparation, Writing?Review and editing; I.T.-A.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; I.K.: Data interpretation, Writing?Review and editing; O.P.: Data interpretation, Writing?Review and editing; L.N.: Data interpretation, Writing?Review and editing; T.S.; Conceptualization, Data interpretation, Writing?Review and editing; C.M.: Conceptualization, Data interpretation, Writing?Review and editing; G.L.: Conceptualization, Supervision, Data interpretation, Writing?Original draft preparation, Writing?Review and editing. A patent covering all the main aspects of the use of IgG glycome as a predictor of menopause and perimenopause has been filed by Genos Ltd (application number: P20210509A). The application is currently pending. D.K. C.M. and G.L. are named as co-inventors on the patent application. G.L. is the founder and owner of Genos Ltd, a biotech company specializing in high-throughput glycomics that also has several patents in the field. H.D. A.Ci. T.P. and I.T.-A. are employees of Genos Ltd. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = mar,

day = "18",

doi = "10.1016/j.isci.2022.103897",

language = "English",

volume = "25",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier publishing company",

number = "3",

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TY - JOUR

T1 - Immunoglobulin G glycome composition in transition from premenopause to postmenopause

AU - Deriš, Helena

AU - Kifer, Domagoj

AU - Cindrić, Ana

AU - Petrović, Tea

AU - Cvetko, Ana

AU - Trbojević-Akmačić, Irena

AU - Kolčić, Ivana

AU - Polašek, Ozren

AU - Newson, Louise

AU - Spector, Tim

AU - Menni, Cristina

AU - Lauc, Gordan

N1 - Funding Information: This study has been supported by the European Structural and Investment Funds IRI “CardioMetabolic” grant ( #KK.01.2.1.02.0321 ), Center of Competence in Molecular Diagnostics grant ( #KK.01.2.2.03.0006 ), and Croatian National Center of Research Excellence in Personalized Healthcare grant ( #KK.01.1.1.01.0010 ) and the Human Glycome Project. Equipment and products from Waters and New England Biolabs were used for this research. The Department of Twin Research receives support from grants from the Wellcome Trust ( 212904/Z/18/Z ) and the Medical Research Council (MRC)/ British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1 ), European Union , Chronic Disease Research Foundation (CDRF), Zoe Global Ltd., the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy’|'s and St Thomas' NHS Foundation Trust in partnership with King’|'s College London). C.M. is funded by the Chronic Disease Research Foundation and by the MRC AIM-HY project grant. Funding Information: This study has been supported by the European Structural and Investment Funds IRI ?CardioMetabolic? grant (#KK.01.2.1.02.0321), Center of Competence in Molecular Diagnostics grant (#KK.01.2.2.03.0006), and Croatian National Center of Research Excellence in Personalized Healthcare grant (#KK.01.1.1.01.0010) and the Human Glycome Project. Equipment and products from Waters and New England Biolabs were used for this research. The Department of Twin Research receives support from grants from the Wellcome Trust (212904/Z/18/Z) and the Medical Research Council (MRC)/British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1), European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd. the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy?|'s and St Thomas' NHS Foundation Trust in partnership with King?|'s College London). C.M. is funded by the Chronic Disease Research Foundation and by the MRC AIM-HY project grant. D.K.: Data analysis and interpretation, Visualization, Writing?Original draft preparation, Writing?Review and editing; H.D.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; A.Ci.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; T.P.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; A.Cv.: Quantification of IgG N-glycans, Data interpretation, Writing?Original draft preparation, Writing?Review and editing; I.T.-A.: Quantification of IgG N-glycans, Data interpretation, Writing?Review and editing; I.K.: Data interpretation, Writing?Review and editing; O.P.: Data interpretation, Writing?Review and editing; L.N.: Data interpretation, Writing?Review and editing; T.S.; Conceptualization, Data interpretation, Writing?Review and editing; C.M.: Conceptualization, Data interpretation, Writing?Review and editing; G.L.: Conceptualization, Supervision, Data interpretation, Writing?Original draft preparation, Writing?Review and editing. A patent covering all the main aspects of the use of IgG glycome as a predictor of menopause and perimenopause has been filed by Genos Ltd (application number: P20210509A). The application is currently pending. D.K. C.M. and G.L. are named as co-inventors on the patent application. G.L. is the founder and owner of Genos Ltd, a biotech company specializing in high-throughput glycomics that also has several patents in the field. H.D. A.Ci. T.P. and I.T.-A. are employees of Genos Ltd. The remaining authors declare no competing interests. Publisher Copyright: © 2022 The Author(s)

PY - 2022/3/18

Y1 - 2022/3/18

N2 - Gonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043–0.059, p < 0.001) and decrease in digalactosylated (−0.043/yr; 95%CI = −0.050 to −0.037, p < 0.001) and monosialylated glycans (−0.029/yr; 95%CI = −0.034 to −0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.

AB - Gonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043–0.059, p < 0.001) and decrease in digalactosylated (−0.043/yr; 95%CI = −0.050 to −0.037, p < 0.001) and monosialylated glycans (−0.029/yr; 95%CI = −0.034 to −0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.

KW - Glycomics

KW - Molecular biology

KW - Reproductive medicine

UR - http://www.scopus.com/inward/record.url?scp=85125182856&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2022.103897

DO - 10.1016/j.isci.2022.103897

M3 - Article

AN - SCOPUS:85125182856

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 3

M1 - 103897

ER -

Immunoglobulin G glycome composition in transition from premenopause to postmenopause

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