SinoXivThe Immunoglobulin G Glycome: A Modifiable Biomarker and Functional Effector of Aging, Disease, and Mortality
Abstract
Glycosylation is a key structural modification of immunoglobulin G (IgG) that modulates its effector functions and has multiple roles in balancing inflammation. Altered IgG glycosylation has been reported in many diseases, often years before clinical manifestation, suggesting its causal role and biomarker potential. Here, we analyzed IgG glycome composition in 20,405 individuals from 42 different studies processed at the Genos Glycoscience Research Laboratory between 2008 and 2025. Across nearly all diseases, specific IgG glycome profiles reflected accelerated biological aging. Accelerated glycan aging was strongly associated with increased risk of all-cause mortality, independent of established clinical risk factors and potential confounders. Moreover, interventions known to reduce mortality risk, including hormone replacement therapy, therapeutic plasma exchange and caloric restriction, were associated with reversal of glycan aging. Given their role in modulating low-grade systemic inflammation, IgG glycans may represent a functional link between chronic inflammation, aging, disease susceptibility and all-cause mortality.
Keywords
Citation Information
@article{gordanlauc2026,
title={The Immunoglobulin G Glycome: A Modifiable Biomarker and Functional Effector of Aging, Disease, and Mortality},
author={Gordan Lauc and Anika Mijakovac and Elena Butz and Frano Vuckovic and Azra Frkatović-Hodžić and Domagoj Kifer and Helena Deris and Barbara Radovani and Fran Lukšić and Ana Cindric and Ivan Gudelj and Nina Šimunić Briški and Goran Josipović and Zehra Stara Yuksel and Jasmina Ćatić and Fran Šaler and Janko Szavits-Nossan and Charlotte Hedin and Jelena Šimunović and Iwona Borošak and Jasminka Kristic and Sara Monteiro-Martins and Tea Pribić and Maja Hanić and Maja Pučić-Baković and Irena Trbojević-Akmačić and Tamara Štambuk and Jerko Štambuk and Marina Martinić Kavur and Matko Fančović and Ana cvetko and Marija Pezer and Ozren Polašek and Olga Gornik and Dobri Kiprov and Eric Verdin and Brad Younggren and Louise Newson and Cristina Menni and Claire Steves and Tim Spector and Jonas Halfvarsson and Ewa Pochec and Marta Zabczynska and Mirjana Turkalj and James Wilson and Marta Alarcon-Riquelme and Konrad Aden and Philip Rosenstiel and Andre Franke and Norbert Frey and Stefan Schreiber and Ellen Blaak and Anna Köttgen and Vlatka Zoldoš and Dragan Primorac and Damir Marjanović and Ulla Schultheiss and Wei Wang and Borna Rapčan},
journal={Research Square},
year={2026},
doi={https://doi.org/10.21203/rs.3.rs-9488315/v1}
}
