Protein Mannosylation as a Diagnostic and Prognostic Biomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic Lupus Erythematosus.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
19
11
2020
accepted:
08
04
2021
pubmed:
22
4
2021
medline:
16
12
2021
entrez:
21
4
2021
Statut:
ppublish
Résumé
Changes in protein glycosylation are a hallmark of immune-mediated diseases. Glycans are master regulators of the inflammatory response and are important molecules in self-nonself discrimination. This study was undertaken to investigate whether lupus nephritis (LN) exhibits altered cellular glycosylation to identify a unique glycosignature that characterizes LN pathogenesis. A comprehensive tissue glycomics characterization was performed in kidney specimens from patients with systemic lupus erythematosus and biopsy-proven LN. A combination of advanced tissue mass spectrometry, in situ glyco-characterization, and ex vivo glycophenotyping was performed to structurally map the repertoire of N-glycans in LN tissue samples. LN exhibited a unique glycan signature characterized by increased abundance and spatial distribution of unusual mannose-enriched glycans that are typically found in lower microorganisms. This glycosignature was specific for LN, as it was not observed in other kidney diseases. Exposure of mannosylated glycans in LN was shown to occur at the cell surface of kidney cells, promoting increased recognition by specific glycan-recognizing receptors expressed by immune cells. This abnormal glycosignature of LN was shown to be due to a deficient complex N-glycosylation pathway and a proficient O-mannosylation pathway. Moreover, mannosylation levels detected in kidney biopsy samples from patients with LN at the time of diagnosis were demonstrated to predict the development of chronic kidney disease (CKD) with 93% specificity. Cellular mannosylation is a marker of LN, predicting the development of CKD, and thus representing a potential glycobiomarker to be included in the diagnostic and prognostic algorithm of LN.
Substances chimiques
Biomarkers
0
Polysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2069-2077Subventions
Organisme : Centre National de la Recherche Scientifique
ID : ANR-10-INBS-05-02
Organisme : Centre National de la Recherche Scientifique
ID : ANR-15-IDEX-02
Organisme : Centre National de la Recherche Scientifique
ID : ANR-17-EURE-0003
Organisme : Centre National de la Recherche Scientifique
ID : UMS 3518 CNRS-CEA-UGA-EMBL
Organisme : Fundação para a Ciência e a Tecnologia
ID : PD/BD/135452/2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : POCI-01-0145-FEDER-028772
Organisme : Fundação para a Ciência e a Tecnologia
ID : POCI-01/ 0145-FEDER-016601
Organisme : Fundação para a Ciência e a Tecnologia
ID : PTDC/DTP-PIC/0560/2014
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BD/128874/2017
Informations de copyright
© 2021, American College of Rheumatology.
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