Muscle glycome in idiopathic inflammatory myopathies: Impact in IL-6 production and disease prognosis
Ana Campar,
Inês Alves,
Beatriz Santos-Pereira,
Rafaela Nogueira,
Miguel Mendonça Pinto,
Carlos Vasconcelos,
Salomé S. Pinho
Affiliations
Ana Campar
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Clinical Immunology Unit, Porto University Hospital Centre, Porto, Portugal
Inês Alves
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
Beatriz Santos-Pereira
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal
Rafaela Nogueira
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Department of Chemistry, NOVA School of Science and Technology, Lisbon, Portugal
Miguel Mendonça Pinto
Neuropathology Department, Porto University Hospital Centre, Porto, Portugal
Carlos Vasconcelos
Clinical Immunology Unit, Porto University Hospital Centre, Porto, Portugal
Salomé S. Pinho
Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; Corresponding author
Summary: 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.