TY - JOUR
T1 - Revisiting the immunopathology of congenital disorders of glycosylation
T2 - an updated review
AU - Pascoal, Carlota
AU - Francisco, Rita
AU - Mexia, Patrícia
AU - Pereira, Beatriz Luís
AU - Granjo, Pedro
AU - Coelho, Helena
AU - Barbosa, Mariana
AU - dos Reis Ferreira, Vanessa
AU - Videira, Paula Alexandra
N1 - info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT#
info:eu-repo/grantAgreement/EC/H2020/825575/EU#
info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F138647%2F2018/PT#
info:eu-repo/grantAgreement/FCT/CEEC IND 3ed/2020.03261.CEECIND%2FCP1586%2FCT0012/PT#
info:eu-repo/grantAgreement/FCT/Concurso de Projetos de Investigação de Caráter Exploratório (PeX) em Todos os Domínios Científicos/EXPL%2FQUI-OUT%2F0069%2F2021/PT#
info:eu-repo/grantAgreement/FCT/Concurso de Projetos de I&D em Todos os Domínios Científicos - 2022/2022.04607.PTDC/PT#
The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work received financial support from the European Commission through the GLYCOTwinning project (Grant Pascoal et al. 10.3389/fimmu.2024.1350101 Frontiers in Immunology 16 frontiersin.org Agreement: 101079417). CP thanks FCT for the grant. BP (EJPRD/0001/2020/ B2) thanks EJPRD COFUND-EJP N 825575 for her fellowship through the ProDGNE project (EJPRD/0001/2020). PG thanks the CDG & Allies – Professionals and Patient Associations International Network for the 9th Liliana Scientific Initiation Scholarship. HC thanks FCT for the CEEC the funding project 2023.00074.RESTART.
Publisher Copyright:
Copyright © 2024 Pascoal, Francisco, Mexia, Pereira, Granjo, Coelho, Barbosa, dos Reis Ferreira and Videira.
PY - 2024
Y1 - 2024
N2 - Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG.
AB - Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG.
KW - cell adhesion molecules
KW - congenital disorders of glycosylation
KW - host-pathogen interactions
KW - immune response
KW - inborn errors of immunity
KW - PMM2-CDG
UR - http://www.scopus.com/inward/record.url?scp=85188965050&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1350101
DO - 10.3389/fimmu.2024.1350101
M3 - Review article
C2 - 38550576
AN - SCOPUS:85188965050
SN - 1664-3224
VL - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1350101
ER -