Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis

ABSTRACT Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (...

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Autores principales:	Noortje de Haan, Navin P. Boeddha, Ebru Ekinci, Karli R. Reiding, Marieke Emonts, Jan A. Hazelzet, Manfred Wuhrer, Gertjan J. Driessen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	children critical care Fc glycosylation immunoglobulin G meningococcal sepsis N-glycan Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bcf1a7b529ae4c47a91e849879ad7a47
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spelling	oai:doaj.org-article:bcf1a7b529ae4c47a91e849879ad7a472021-11-15T16:00:25ZDifferences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis10.1128/mBio.00546-182150-7511https://doaj.org/article/bcf1a7b529ae4c47a91e849879ad7a472018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00546-18https://doaj.org/toc/2150-7511ABSTRACT Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome. IMPORTANCE Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the N-glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor.Noortje de HaanNavin P. BoeddhaEbru EkinciKarli R. ReidingMarieke EmontsJan A. HazelzetManfred WuhrerGertjan J. DriessenAmerican Society for Microbiologyarticlechildrencritical careFc glycosylationimmunoglobulin Gmeningococcal sepsisN-glycanMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	children critical care Fc glycosylation immunoglobulin G meningococcal sepsis N-glycan Microbiology QR1-502
spellingShingle	children critical care Fc glycosylation immunoglobulin G meningococcal sepsis N-glycan Microbiology QR1-502 Noortje de Haan Navin P. Boeddha Ebru Ekinci Karli R. Reiding Marieke Emonts Jan A. Hazelzet Manfred Wuhrer Gertjan J. Driessen Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
description	ABSTRACT Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome. IMPORTANCE Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the N-glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor.
format	article
author	Noortje de Haan Navin P. Boeddha Ebru Ekinci Karli R. Reiding Marieke Emonts Jan A. Hazelzet Manfred Wuhrer Gertjan J. Driessen
author_facet	Noortje de Haan Navin P. Boeddha Ebru Ekinci Karli R. Reiding Marieke Emonts Jan A. Hazelzet Manfred Wuhrer Gertjan J. Driessen
author_sort	Noortje de Haan
title	Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
title_short	Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
title_full	Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
title_fullStr	Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
title_full_unstemmed	Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis
title_sort	differences in igg fc glycosylation are associated with outcome of pediatric meningococcal sepsis
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/bcf1a7b529ae4c47a91e849879ad7a47
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Differences in IgG Fc Glycosylation Are Associated with Outcome of Pediatric Meningococcal Sepsis

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