TY - JOUR
T1 - Muscle glycome in idiopathic inflammatory myopathies
T2 - Impact in IL-6 production and disease prognosis
AU - Campar, Ana
AU - Alves, Inês
AU - Santos-Pereira, Beatriz
AU - Nogueira, Rafaela
AU - Pinto, Miguel Mendonça
AU - Vasconcelos, Carlos
AU - Pinho, Salomé S.
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/CEEC IND5ed/2022.00337.CEECIND%2FCP1735%2FCT0014/PT#
Funding: Supported by the Portugal 2020 Partnership Agreement’s Norte Portugal Regional Programme (NORTE 2020) (project NORTE-01-0145-FEDER-000029 ), Fundo Europeu de Desenvolvimento Regional (FEDER) funds from the Compete2020 Science, Technology, and Innovation Operational Programme (POCI), and the Portuguese Foundation for Science and Technology (FCT) (projects POCI-01/0145-FEDER-016601 and POCI-01-0145-FEDER-028772 ). A.C. work was supported by the Portuguese Society of Internal Medicine’s Group for Study of Autoimmune Diseases ( NEDAI ). I.A. and S.S.P. were also funded by Clinical Research in Autoimmunity prize (supported by National Medical Association in Autoimmunity (NEDAI) and National Society of Internal Medicine (SPMI)) and Pfizer prize (supported by Pfizer and Society of Medical Sciences of Lisbon ).
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7/21
Y1 - 2023/7/21
N2 - Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune diseases mainly affecting proximal muscles. Absence of meaningful prognostic factors in IIM has hindered new therapies development. Glycans are essential molecules that regulate immunological tolerance and consequently the onset of autoreactive immune response. We showed that muscle biopsies from patients with IIM revealed a deficiency in the glycosylation pathway resulting in loss of branched N-glycans. At diagnosis, this glycosignature predicted disease relapse and treatment refractoriness. Peripheral CD4+ T cells from active-disease patients shown a deficiency in branched N-glycans, linked to increased IL-6 production. Glycan supplementation, restoring homeostatic glycosylation profile, led to a decrease in IL-6 levels. This study highlights the biological and clinical importance of glycosylation in IIM immunopathogenesis, providing a potential mechanism for IL-6 production. This pinpoints muscle glycome as promising biomarker for personalized follow-up and a potential target for new therapies in a patients’ subgroup with an ominous evolution.
AB - Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune diseases mainly affecting proximal muscles. Absence of meaningful prognostic factors in IIM has hindered new therapies development. Glycans are essential molecules that regulate immunological tolerance and consequently the onset of autoreactive immune response. We showed that muscle biopsies from patients with IIM revealed a deficiency in the glycosylation pathway resulting in loss of branched N-glycans. At diagnosis, this glycosignature predicted disease relapse and treatment refractoriness. Peripheral CD4+ T cells from active-disease patients shown a deficiency in branched N-glycans, linked to increased IL-6 production. Glycan supplementation, restoring homeostatic glycosylation profile, led to a decrease in IL-6 levels. This study highlights the biological and clinical importance of glycosylation in IIM immunopathogenesis, providing a potential mechanism for IL-6 production. This pinpoints muscle glycome as promising biomarker for personalized follow-up and a potential target for new therapies in a patients’ subgroup with an ominous evolution.
KW - Disease
KW - Glycobiology
KW - Glycomics
KW - Health sciences
UR - http://www.scopus.com/inward/record.url?scp=85163854746&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.107172
DO - 10.1016/j.isci.2023.107172
M3 - Article
C2 - 37404372
AN - SCOPUS:85163854746
SN - 2589-0042
VL - 26
JO - ISCIENCE
JF - ISCIENCE
IS - 7
M1 - 107172
ER -