Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Corona-Sánchez, Esther Guadalupe; Martínez-García, Erika Aurora; Lujano-Benítez, Andrea Verónica; Pizano-Martínez, Óscar; Guerra-Durán, Ivette Alejandra; Chavarria-Ávila, Efraín; Aguilar-Vazquez, Andrea; Martín-Márquez, Beatriz Teresita; Arellano-Arteaga, Kevin Javier; Armendáriz‐Borunda, Juan; Perez-Vazquez, Felipe; Torre, Ignacio García‐De La; Llamas-García, Arcelia; Palacios-Zárate, Brenda Lucía; Toriz-González, Guillermo; Mercado, Mónica Vázquez-Del

doi:10.3389/fimmu.2022.940122

Cited by 7 publications

(4 citation statements)

References 175 publications

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“…Hypotheses on the pathogenesis of IIM have been proposed as endoplasmic reticulum stress, vasculopathy, acquired interferonopathy, and so on (8)(9)(10). In the blood, skin, and muscles of IIM, upregulation of the IFN pathway has been verified and can reflect disease activity (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies

Zhang

et al. 2023

Front. Immunol.

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BackgroundMyositis-specific autoantibodies (MSAs) are clinically used to diagnose and define idiopathic inflammatory myopathy (IIM) subsets. However, the underlying pathogenic mechanisms of patients with different MSAs remain unclear.MethodsA total of 158 Chinese patients with IIM and 167 gender- and age-matched healthy controls (HCs) were enrolled. Transcriptome sequencing (RNA-Seq) was performed with peripheral blood mononuclear cells (PBMCs), followed by the identification of differentially expressed genes (DEGs) and analysis of gene set enrichment analysis, immune cell infiltration, and WGCNA. Monocyte subsets and related cytokines/chemokines were quantified. The expressions of interferon (IFN)-related genes were validated using qRT-PCR and Western blot in both PBMCs and monocytes. We also performed correlation analysis and ROC analysis to explore the potential clinical significance of the IFN-related genes.ResultsThere were 1,364 genes altered in patients with IIM, including 952 upregulated and 412 downregulated genes. The type I interferon (IFN-I) pathway was remarkably activated in patients with IIM. Compared with patients with other MSAs, IFN-I signatures were significantly activated in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. In total, 1,288 hub genes associated with IIM onset were identified using WGCNA, including 29 key DEGs associated with IFN signaling. The patients had more CD14brightCD16- classical, CD14brightCD16+ intermediate, and fewer CD14dimCD16+ non-classical monocyte subsets. Plasma cytokines like IL-6 and TNF and chemokines including CCL3 and MCPs increased. The validation of IFN-I-related gene expressions was consistent with the findings from RNA-Seq. The IFN-related genes were correlated with laboratory parameters and helpful for IIM diagnosis.ConclusionGene expressions were remarkably altered in the PBMCs of IIM patients. Anti-MDA5+ IIM patients had a more pronounced activated IFN signature than others. Monocytes exhibited a proinflammatory feature and contributed to the IFN signature of IIM patients.

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Section: Introductionmentioning

confidence: 99%

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies

Zhang

et al. 2023

Front. Immunol.

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“…У части пациентов могут преобладать внемышечные признаки, такие как кожная сыпь, артрит, интерстициальные заболевания легких (ИЗЛ), поражение сердца, при этом мышечная слабость может быть мало выраженной или отсутствовать [2,3], что затрудняет своевременную диагностику заболевания в целом. Полагают, что в основе фенотипического разнообразия ИВМ лежат различные патофизиологические механизмы повреждения мышц, маркерами которых могут служить миозитспецифические (МСА) и миозит-ассоциированные (МАА) аутоантитела [4,5]. МСА информативны в определении вариантов ИВМ, а также в оценке прогноза.…”

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Capabilities of magnetic resonance imaging in the diagnosis of idiopathic inflammatory myopathies

Kolomeychuk

2024

Naučno-praktičeskaâ revmatologiâ

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Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune conditions characterized by proximal muscle weakness and potentially accompanied by a range of extramuscular clinical manifestations. There are subtypes of IIM including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), overlap myositis (OM) with subgroup of anti-synthetase syndrome (ASS) and cancer-associated myositis. Taking into account rarity of the disease, heterogeneity of clinical presentation, difficulties in detection methods and interpretation of myositis associated autoantibodies (MAAs) and myositis specific autoantibodies (MSAs), search for objective imaging methods of muscle damage continues. This is important to definitive diagnosis, predicting subtypes of IIM and case follow-up. One of the most promising methods is magnetic resonance imaging (MRI). The aim of the review was to examine the role of MRI in assessment muscle damage, in particular, most typical MRI-findings and there features in different types of IIM with further clinical cases.

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“…Oxidative stress and cytokines are widely involved in DM pathophysiology and are believed to be crucial for the regulation of mitochondrial function. 4,5 Mitochondrial abnormalities, including increased ROS production and decreased respiration, have been correlated with low exercise capacity and a type I IFN signature. Zhao et al 6 reported that mitochondrial D-loop SNPs could be potential biomarkers for DM risk.…”

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“…[8][9][10][11] The d-ROM values were also associated with idiopathic pulmonary fibrosis (IPF), oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and other abnormalities. 1,5,7 These factors may affect d-ROM levels in dermatomyositis. In addition, we should evaluate the d-ROM levels between intra-patient d-ROMs and not inter-patient d-ROMs.…”

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confidence: 99%

Oxidative stress and dermatomyositis: Report of d‐ROM measurements in 13 cases

Matsuo,

Tawada,

Tanaka

et al. 2023

Int J of Rheum Dis

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Oxidative stress and dermatomyositis: Report of d-ROM measurements in 13 casesDear Editor, Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signaling in the skeletal muscles and skin. 1 Type I IFN-stimulated gene (ISG15), interferon alpha inducible protein 6 (IFI6), and MX dynamin like GTPase 1 (MX1), are also overexpressed in DM. 2 Cytokines and oxidative stress are both widely involved in DM pathophysiology, and evidence is mounting that reactive oxygen species (ROS) play a key role in skeletal muscle weakness in DM. 3,4 However, ROS are very unstable in nature and are difficult to detect directly. The test for diacron-reactive oxygen metabolites (d-ROMs) detects hydroperoxides (ROOH), which are oxygen metabolites of lipids, proteins, amino acids, and nucleic acids. Hydroperoxides are highly stable even in stored samples. This study examined the relationship between DM and oxidative stress and how it differs before versus after treatment. We measured d-ROMs from the sera of 13 patients who first visited our hospital and received systemic corticosteroids as monotherapy or in combination with immunosuppressive agents between 2014 and 2018. This study was approved by the Ethics Committee of Gifu University (#2022-135). Serum d-ROM levels were evaluated before and after treatment. The d-ROM test measures metabolites produced by ROS in a sample by the colorimetric change of a chromogen. The d-ROM value is determined by the Free Radical Electron Evaluator (RE-DOXLIBRA; WISMERLL). According to the manufacturer's instructions, the oxidative stress that corresponds to each range of d-ROM values

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Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Cited by 7 publications

References 175 publications

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies

Type 1 interferon signature in peripheral blood mononuclear cells and monocytes of idiopathic inflammatory myopathy patients with different myositis-specific autoantibodies

Capabilities of magnetic resonance imaging in the diagnosis of idiopathic inflammatory myopathies

Oxidative stress and dermatomyositis: Report of d‐ROM measurements in 13 cases

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