IgG1 Fc N-glycan galactosylation as a biomarker for immune activation

Sanne E De Jong,Alejandro Rodriguez,Philip J Cooper,Daniel Boakye,Cornelis H Hokke,Manfred Wuhrer,Yvonne C M Kruize,Maurice H J Selman,Erika Von Mutius,Ayola A Adegnika,John G Raynes,Jon Genuneit,André C Knulst,Elly Van Riet,Maria Yazdanbakhsh,Abena S Amoah

doi:10.1038/srep28207

Abstract

Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases.

Highlights

ZBMIa activation of immune cells by pathogen-associated molecular patterns and foreign antigens[9]
This study shows that galactosylation of IgG1 Fc N-glycans varies considerably between affluent and developing countries and between urban and rural communities in the same country, where lower galactosylation levels are seen in less affluent countries and in more rural communities
Regarding factors that could explain this pattern, when considering all study participants, a negative correlation was found between C-reactive protein (CRP) levels, a marker of inflammation, and IgG1 galactosylation levels

Summary

Introduction

ZBMIa activation of immune cells by pathogen-associated molecular patterns and foreign antigens[9]. Many non-communicable diseases that are seen in affluent countries or upon urbanisation are associated with tissue inflammation. These diseases might result from triggering of the immune system by a different array of stimuli such as damage-associated molecular patterns, self-antigens, and/or allergens[10]. This raises the question how IgG glycosylation patterns differ with infection pressure and with affluence and urbanisation. It is possible that IgG glycosylation patterns could provide a biomarker of immune activation in the context of urbanisation, which is a much needed tool for epidemiological studies

Methods

Results

Conclusion