Campar Ana, Alves Inês, Santos-Pereira Beatriz, Nogueira Rafaela, Pinto Miguel Mendonça, Vasconcelos Carlos, Pinho Salomé S
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.
iScience. 2023 Jun 17;26(7):107172. doi: 10.1016/j.isci.2023.107172. eCollection 2023 Jul 21.
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 -glycans. At diagnosis, this glycosignature predicted disease relapse and treatment refractoriness. Peripheral CD4 T cells from active-disease patients shown a deficiency in branched -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.
特发性炎性肌病（IIM）是一组主要影响近端肌肉的慢性自身免疫性疾病。IIM中缺乏有意义的预后因素阻碍了新疗法的开发。聚糖是调节免疫耐受并因此调节自身反应性免疫反应发生的重要分子。我们发现，IIM患者的肌肉活检显示糖基化途径存在缺陷，导致分支聚糖缺失。在诊断时，这种糖基特征可预测疾病复发和治疗难治性。活动性疾病患者的外周血CD4 T细胞显示分支聚糖缺乏，这与IL-6产生增加有关。补充聚糖可恢复稳态糖基化谱，导致IL-6水平降低。这项研究突出了糖基化在IIM免疫发病机制中的生物学和临床重要性，为IL-6的产生提供了一种潜在机制。这表明肌肉糖组有望成为个性化随访的生物标志物，也是具有不良病情发展的患者亚组新疗法的潜在靶点。
