Global variability of the human IgG glycome

Štambuk, Jerko; Nakić, Natali; Vučković, Frano; Pučić‐Baković, Maja; Razdorov, Genadij; Trbojević‐Akmačić, Irena; Novokmet, Mislav; Keser, Toma; Vilaj, Marija; Štambuk, Tamara; Gudelj, Ivan; Šimurina, Mirna; Song, Manshu; Wang, Hao; Salihović, Marijana Peričić; Campbell, Harry; Rudan, Igor; Kolčić, Ivana; Eller, Leigh Anne; McKeigue, Paul; Robb, Merlin L.; Halfvarson, Jonas; Kurtoğlu, Metin; Annese, Vito; Škarić‐Jurić, Tatjana; Molokhia, Mariam; Polašek, Ozren; Hayward, Caroline; Kibuuka, Hannah; Thaqi, Kujtim; Primorac, Dragan; Gieger, Christian; Nitayaphan, Sorachai; Spector, Tim D.; Wang, Youxin; Tillin, Therese; Chaturvedi, Nish; Wilson, James F.; Schanfield, Moses S.; Филипенко, М. Л.; Wang, Wei; Lauc, Gordan

doi:10.18632/aging.103884

Cited by 50 publications

(38 citation statements)

References 66 publications

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“…Previous population studies revealed that IgG N-glycome composition changes with age, especially in females in the time preceding the average age of menopause 17,18 . In this study we used multiple samples from the same individuals to confirm the association between perimenopause and the extensive changes in the IgG glycome composition.…”

Section: Discussionmentioning

confidence: 99%

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Immunoglobulin G glycome composition in transition from pre-menopause to menopause

Kifer

Deriš

Cindrić

et al. 2021

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Background Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and its changes are believed to be a significant contributor to inflammaging. Gonadal hormones affect IgG glycome composition, suggesting that alterations in IgG glycosylation might be one of the molecular mechanisms behind increased disease risk in perimenopause. Methods IgG was isolated from 5,354 plasma samples collected from 1,940 females and 113 males at multiple time points. IgG glycans were released, labelled with a fluorescent dye and analysed by ultra-high-performance liquid chromatography. Mixed modelling was used to determine average levels of individual IgG glycans in pre-menopausal women, menopausal women, and men. Findings Large and statistically significant differences in IgG glycome composition were observed, mainly reflecting decreased galactosylation and sialylation of glycans in menopausal women. During perimenopause women had a significant higher 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 - -0.037, p<0.001), and monosialylated glycans (-0.029/yr; 95%CI = -0.034 - -0.024, p<0.001), compared to premenopausal women. Interpretation 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. IgG glycome changes considerably during perimenopause and may aid the diagnosis of perimenopause. Funding Croatian National Centre of Excellence in Personalised Healthcare, ESI Funds grant for the Centre of Competences in Molecular Diagnostics, the Wellcome Trust and the Medical Research Council (MRC)/British Heart Foundation (BHF).

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Section: Discussionmentioning

confidence: 99%

“…Large population studies revealed that IgG glycome composition changes with age and that in females this change is particularly pronounced in the time preceding the average age of menopause 17,18 . However, the association between changes in the IgG glycome composition and menopause has not yet been validated.…”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin G glycome composition in transition from pre-menopause to menopause

Kifer

Deriš

Cindrić

et al. 2021

Preprint

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“…On the other hand, the levels of digalactosylated (G2) glycans increased after bariatric surgery and at sequential timepoints, in accordance with a reduced inflammatory potential of the circulating IgG. The increased levels of IgG galactosylation were previously associated with a younger biological age and are considered, in a way, as a measure of an individual’s well-being [9,12]. Converesely, IgG galactosylation levels substantially decrease with ageing and during inflammation [9,11].…”

Section: Discussionmentioning

confidence: 99%

“…Progressive age-related changes of IgG glycosylation have been extensively studied [7,9,10] and the GlycanAge model has been proposed to express the difference between chronological and IgG glycome ageing [11]. The age of the IgG glycome might be estimated through the levels of agalactosylated species, which increase with ageing and are associated with enhanced immune activation [12]. The opposite applies for digalactosylated IgG glycoforms, which are usually related to a younger age.…”

Section: Introductionmentioning

confidence: 99%

Extensive weight loss can reduce immune age by altering IgG N-glycosylation

Greto

Cvetko

Štambuk

et al. 2020

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“…It is known that IgG glycosylation changes as a function of age in individuals from the general population 28,40 . Our observations of IgG glycosylation in healthy non-DS individuals from the general populations (who served as age-, sex-and, when possible, demography-matched controls for persons with DS) con rmed the previously reported increase in levels of G0 and B IgG as well as decrease in levels of G2 and S IgG glycans with increasing age (Figure 4 and Supplementary Table 5).…”

Section: The Relationship Between Igg Glycosylation and Age In Persons With Down Syndromementioning

confidence: 99%

Accelerated biological aging in people with Down syndrome with full and segmental trisomy 21 begins in childhood as revealed by immunoglobulin G glycosylation

Cindrić

Vučković

Koschut

et al. 2021

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Cells from people with Down syndrome (DS) show faster accumulation of DNA damage and epigenetic aging marks. Causative mechanisms remain un-proven and hypotheses range from amplified chromosomal instability to actions of several supernumerary chromosome 21 genes. Plasma immunoglobulin G (IgG) glycosylation profiles are established as a reliable predictor of biological and chronological aging. We performed IgG glycan profiling of n=246 individuals with DS (208 adults and 38 children) from three European populations and compared these to age-, sex- and demography-matched general populations. We uncovered very significantly increased IgG glycosylation aging marks associated with DS. Average levels of IgG glycans without galactose (G0) and those with two galactoses (G2) as a function of age in persons with DS corresponded to levels detected in 19 years older euploid individuals. Some aging marks were significant already in children with DS. Remarkably, the IgG glycan profiles of a child with segmental duplication of only 31 genes on chromosome 21 had values similar to those of age-matched DS children, outside the normal children’s range. This is the first non-epigenetic evidence of accelerated systemic biological aging in DS, suggesting it begins very early in childhood. It points to a causative contribution of the overdose of genes in a short segment of chromosome 21, not previously linked to accelerated aging, opening a route to discovery of hitherto unrecognised mechanisms.

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Global variability of the human IgG glycome

Cited by 50 publications

References 66 publications

Immunoglobulin G glycome composition in transition from pre-menopause to menopause

Immunoglobulin G glycome composition in transition from pre-menopause to menopause

Extensive weight loss can reduce immune age by altering IgG N-glycosylation

Accelerated biological aging in people with Down syndrome with full and segmental trisomy 21 begins in childhood as revealed by immunoglobulin G glycosylation

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