Global variability of the human IgG glycome

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

Mar 04, 2019

Received Date: 14th February 19

Immunoglobulin G (IgG) is the most abundant serum antibody and is a key determinant of the humoral immune response. Its structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. IgG N-glycome patterns change with the age of individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is affected by a combination of genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of whole IgG, analysed in 5 different populations totalling 10,482 IgG glycomes, and of IgG’s fragment crystallisable region (Fc), analysed in 2,530 samples from 27 populations sampled across the world. We observed that country of residence associates with many N-glycan features and is a strong predictor of monogalactosylation variability. IgG galactosylation also strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators. We found that subjects from developing countries had low IgG galactosylation levels, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to country-specific environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature