IgG Fc glycosylation as an axis of humoral immunity in childhood

Cheng, Hao; Tirosh, Irit; Haan, Noortje de; Stöckmann, Henning; Adamczyk, B; McManus, Ciara A.; O’Flaherty, Róisín; Greville, Gordon; Saldova, Radka; Bonilla, Francisco A.; Notarangelo, Luigi D.; Holm, Ingrid A.; Rudd, Pauline M.; Wuhrer, Manfred; Ackerman, Margaret E.; Nigrović, Peter A.

doi:10.1016/j.jaci.2019.10.012

Cited by 31 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This shift would predictably affect the antibody interactions with other immune components (e.g. B cells, innate cells, and complement) and function during the first years of life and onwards [14]. This notion is consistent with our current understanding of the programming of the immune system in early life, which adapts to meet environmental demands during fetal life and after birth [2].…”

Section: Interactions Of Maternal Antibodies With the Infant Immune Ssupporting

confidence: 73%

Maternal determinants of infant immunity: Implications for effective immunization and maternal-child health

Pasetti

Ackerman

Hoen

et al. 2020

Vaccine

Self Cite

View full text Add to dashboard Cite

Section: Interactions Of Maternal Antibodies With the Infant Immune Ssupporting

confidence: 73%

Maternal determinants of infant immunity: Implications for effective immunization and maternal-child health

Pasetti

Ackerman

Hoen

et al. 2020

Vaccine

Self Cite

View full text Add to dashboard Cite

“…Glycans attached to IgG are functionally important because they regulate inflammation at multiple levels [15,16] and are considered to be one of the important drivers of inflammaging [17]. Large studies of adult human populations indicated that IgG glycans without galactose and sialic acid that are the main component of the increased glycan age increase with the onset of menopause [1], while in girls they decrease with the onset of puberty [8,18]. This indicated that estrogen may be relevant, but since many things change during puberty and menopause, the change in glycan age could not have been directly attributed to the change in estrogen concentration.…”

Section: Discussionmentioning

confidence: 99%

Effects of estradiol on biological age measured using the glycan age index

Jurić

Kohrt

Kifer

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Glycan age is a recently developed biomarker based on glycans attached to immunoglobulin G (IgG). In large population cohorts glycan age associates well with lifestyle and disease-risk biomarkers, while some studies suggested that change in glycans precede development of several age-associated diseases. In this study we evaluated effects of estrogen on the glycan age. Gonadal hormones were suppressed in 36 healthy young women by gonadotropin releasing hormone agonist therapy for 6 months. In 15 of them estradiol was supplemented, while 21 received placebo resulting in very low estrogen levels during intervention. IgG was isolated from plasma samples before intervention, after 6 months of intervention and after subsequent 4-month recovery. In the placebo group the removal of gonadal hormones resulted in median increase of glycan age for 9.1 years (IQR 6.8 - 11.5 years, p = 3.73x10-8), which was completely prevented by transdermal estradiol supplementation. After the recovery period glycan age returned to baseline values also in the placebo group. These results suggest that IgG glycans and consequently also the glycan age are under strong influence of gonadal hormones and that hormone replacement therapy can prevent the increase of glycan age that occurs in the perimenopausal period.

show abstract

“…Glycosylation strongly influences immunogenicity, half-life, and clinical efficacy of therapeutic proteins [ 7 , 8 ]. Heterogeneity in glycosylation occurring at glycosites in the active protein, the protein linker, and the immunoglobulin Fc domain has functional and pathological implications [ 9 ]. Therefore, precise quantification of glycosylation of a fusion protein is critical for product solubility, stability, pharmacokinetics, pharmacodynamics, bioactivity, immunogenicity, and toxicity [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

O-Glycoproteomic analysis of engineered heavily glycosylated fusion proteins using nanoHILIC-MS

et al. 2022

View full text Add to dashboard Cite

Recombinant protein engineering design affects therapeutic properties including protein efficacy, safety, and immunogenicity. Importantly, glycosylation modulates glycoprotein therapeutic pharmacokinetics, pharmacodynamics, and effector functions. Furthermore, the development of fusion proteins requires in-depth characterization of the protein integrity and its glycosylation to evaluate their critical quality attributes. Fc-fusion proteins can be modified by complex glycosylation on the active peptide, the fragment crystallizable (Fc) domain, and the linker peptides. Moreover, the type of glycosylation and the glycan distribution at a given glycosite depend on the host cell line and the expression system conditions that significantly impact safety and efficacy. Because of the inherent heterogeneity of glycosylation, it is necessary to assign glycan structural detail for glycoprotein quality control. Using conventional reversed-phase LC–MS methods, the different glycoforms at a given glycosite elute over a narrow retention time window, and glycopeptide ionization is suppressed by co-eluting non-modified peptides. To overcome this drawback, we used nanoHILIC-MS to characterize the complex glycosylation of UTI-Fc, a fusion protein that greatly increases the half-life of ulinastatin. By this methodology, we identified and characterized ulinastatin glycopeptides at the Fc domain and linker peptide. The results described herein demonstrate the advantages of nanoHILIC-MS to elucidate glycan features on glycotherapeutics that fail to be detected using traditional reversed-phase glycoproteomics.

show abstract

IgG Fc glycosylation as an axis of humoral immunity in childhood

Cited by 31 publications

References 18 publications

Maternal determinants of infant immunity: Implications for effective immunization and maternal-child health

Maternal determinants of infant immunity: Implications for effective immunization and maternal-child health

Effects of estradiol on biological age measured using the glycan age index

O-Glycoproteomic analysis of engineered heavily glycosylated fusion proteins using nanoHILIC-MS

Contact Info

Product

Resources

About