IgG1 glycosylation highlights premature aging in Down syndrome

BMM Streng; J Van Coillie; JG Wildenbeest; RS Binnendijk; G Smits; G den Hartog; WJ Wang; J Nouta; F Linty; R Visser; M Wuhrer; G Vidarsson; LJ Bont

doi:10.1111/acel.14167

IgG1 glycosylation highlights premature aging in Down syndrome

BMM Streng, J Van Coillie, JG Wildenbeest, RS Binnendijk, G Smits, G den Hartog, WJ Wang, J Nouta, F Linty, R Visser, M Wuhrer, G Vidarsson, LJ Bont^*

^*Corresponding author for this work

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

Abstract

Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti-S IgG1 with age. In contrast, anti-S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules.

Original language	English
Article number	e14167
Number of pages	10
Journal	Aging Cell
Volume	23
Issue number	7
Early online date	15 Apr 2024
DOIs	https://doi.org/10.1111/acel.14167
Publication status	Published - Jul 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Funding

LJB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>\u20AC100,000 per industrial partner) for investigator\u2010initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill & Melinda Gates Foundation. UMCU has received major funding as part of the public private partnership IMI\u2010funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding from Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer. UMCU received minor funding (\u20AC1000\u201325,000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, mAbXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, Genzyme, and Janssen. LJB is the founding chairman of the ReSViNET Foundation. JGW has been an investigator for clinical trials sponsored by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen. All funds have been paid to UMCU. JGW participated in the advisory board of Janssen and Sanofi with fees paid to UMCU. All other authors declare they have no conflicts of interest. This work was supported by ZonMw, The Netherlands Organization for Health Research and Development grant 10430072010004 (LB). Landsteiner foundation for Blood Transfusion Research (LSBR) grants 1721 and 1908 (GV) ZonMW COVID\u201019 grant 10430012010021 (GV).

Funders	Funder number
MedImmune
Pfizer
ZonMw	10430072010004
ZonMw
Landsteiner Foundation for Blood Transfusion Research	1721, 1908, 10430012010021
Landsteiner Foundation for Blood Transfusion Research

Keywords

Aging
Down syndrome
Glycosylation
Immunoglobulin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/acel.14167Licence: CC BY

Aging Cell - 2024 - Streng - IgG1 glycosylation highlights premature aging in Down syndromeFinal published version, 4.75 MBLicence: CC BY

Cite this

@article{5d47b6354f814ea1a99c0be4f9a9ee85,

title = "IgG1 glycosylation highlights premature aging in Down syndrome",

abstract = "Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti-S IgG1 with age. In contrast, anti-S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules.",

keywords = "Aging, Down syndrome, Glycosylation, Immunoglobulin",

author = "BMM Streng and {Van Coillie}, J and JG Wildenbeest and RS Binnendijk and G Smits and {den Hartog}, G and WJ Wang and J Nouta and F Linty and R Visser and M Wuhrer and G Vidarsson and LJ Bont",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.",

year = "2024",

month = jul,

doi = "10.1111/acel.14167",

language = "English",

volume = "23",

journal = "Aging Cell",

issn = "1474-9718",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "7",

}

TY - JOUR

T1 - IgG1 glycosylation highlights premature aging in Down syndrome

AU - Streng, BMM

AU - Van Coillie, J

AU - Wildenbeest, JG

AU - Binnendijk, RS

AU - Smits, G

AU - den Hartog, G

AU - Wang, WJ

AU - Nouta, J

AU - Linty, F

AU - Visser, R

AU - Wuhrer, M

AU - Vidarsson, G

AU - Bont, LJ

PY - 2024/7

Y1 - 2024/7

N2 - Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti-S IgG1 with age. In contrast, anti-S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules.

AB - Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS-CoV-2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti-spike (S) IgG1 glycosylation patterns following SARS-CoV-2 vaccination in DS and healthy controls (HC). Total and anti-Spike IgG1 Fc N-glycan glycoprofiles were measured in non-exposed adults with DS and controls before and after SARS-CoV-2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti-S IgG1 with age. In contrast, anti-S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules.

KW - Aging

KW - Down syndrome

KW - Glycosylation

KW - Immunoglobulin

UR - http://www.scopus.com/inward/record.url?scp=85190837606&partnerID=8YFLogxK

U2 - 10.1111/acel.14167

DO - 10.1111/acel.14167

M3 - Article

C2 - 38616780

SN - 1474-9718

VL - 23

JO - Aging Cell

JF - Aging Cell

IS - 7

M1 - e14167

ER -

IgG1 glycosylation highlights premature aging in Down syndrome

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this