256th ENMC international workshop: Myositis specific and associated autoantibodies (MSA-ab): Amsterdam, The Netherlands, 8-10 October 2021

Allenbach, Yves; Benveniste, Olivier; Bonroy, Carolien; Bossuyt, Xavier; Boyer, Olivier; Casciola‐Rosen, Livia; Chinoy, Hector; Damoiseaux, Jan; Groot, Ingrid de; Lundberg, Ingrid E.; Mammen, Andrew L.; McHugh, Neil; Mischke, Roland; Piette, Yves; Pruijn, Ger J. M.; Rönnelid, Johan; Selva-O’Callaghan, Albert; Stenzel, Werner; Tansley, Sarah; Vencovský, Jiří; Wang, Guochun

doi:10.1016/j.nmd.2022.05.011

Cited by 24 publications

(21 citation statements)

References 89 publications

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“…This morphological pattern can be seen in a number of diverse conditions, including early IBM, 29 polymyositis with mitochondrial abnormalities (PM-mito), 30 HIV myopathies, 31 and overlap myositis from systemic autoimmune rheumatic diseases, such as LM, SjS, SSc. 32 Recent transcriptome study suggested that PM-mito and IBM are inflammatory processes induced by type II interferon. 33 This is compatible with our finding that MxA myofiber expression was mostly absent in muscles with PM-like inflammation, even in biopsies from patients with SLE, suggesting a different etiology than type I interferon activation.…”

Section: Discussionmentioning

confidence: 99%

“…However, the PM‐like inflammation pattern, characterized by predominantly endomysial T‐cell inflammation that surrounds and invades non‐necrotic muscle fibers, 17 still exists as a useful distinguishing feature in muscle biopsies. This morphological pattern can be seen in a number of diverse conditions, including early IBM, 29 polymyositis with mitochondrial abnormalities (PM‐mito), 30 HIV myopathies, 31 and overlap myositis from systemic autoimmune rheumatic diseases, such as LM, SjS, SSc 32 . Recent transcriptome study suggested that PM‐mito and IBM are inflammatory processes induced by type II interferon 33 .…”

Section: Discussionmentioning

confidence: 99%

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Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis

Xing,

Trivedi,

Bitencourt

et al. 2024

Muscle and Nerve

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Introduction/AimsMyxovirus resistance protein A (MxA) is a type I interferon (IFN1) pathway activation marker and MxA sarcoplasmic expression is currently recognized as a highly specific marker for dermatomyositis (DM). However, we have frequently observed endothelial tubuloreticular inclusions (TRI), another surrogate IFN1 activation marker, in a variety of overlap myositides. The aim of this study was to examine MxA expression in those myositides.MethodsWe retrospectively performed MxA immunostaining on a wide range of myositides.ResultsMxA sarcoplasmic expression was present in DM (94.4%, 17/18), active lupus myositis (LM, 80%,16/20), inactive LM (36%, 4/11), antisynthetase syndrome (ASyS, 20%, 2/10), systemic sclerosis (13%, 2/15), Sjogren's syndrome (7.7%, 1/13), and human immunodeficiency virus (HIV) myositis (5.6%, 1/18) and was absent in immune‐mediated necrotizing myopathy (IMNM, 0/16) and hydroxychloroquine myopathy (0/5). The sensitivity and specificity of MxA sarcoplasmic expression for LM and DM combined compared with all other myositides were 84.6% (95% CI: 69.5–94.1) and 92.1 (95% CI: 83.6–97.0), respectively, and superior to TRIs. MxA capillary expression was nonspecific. Histologically, 35% of LM cases demonstrated a unique panfascicular necrotizing myopathy pattern. The remainder of the LM cases had significant morphological overlap with DM/ASyS (20%), IMNM (20%), or polymyositis (15%).DiscussionMxA sarcoplasmic expression is highly prevalent in LM and DM and is a useful marker in differentiating DM and LM from other myositides. LM can manifest in various pathology patterns that need to be differentiated from DM, IMNM, ASyS, and polymyositis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis

Xing,

Trivedi,

Bitencourt

et al. 2024

Muscle and Nerve

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“…Idiopathic inflammatory myopathies (IIM), also named myositis, are a group of heterogeneous rare diseases characterised by muscle weakness and muscle histopathological features that include the presence of inflammatory infiltrates and myofibre necrosis/ regeneration [1]. The discovery of a variety of myositis-specific or myositis-associated antibodies has provided tools for a better diagnosis and evaluation of the prognosis of myositis [2]. Yet, despite recent advances, a substantial proportion of patients do not display any known myositis-associated antibodies [3].…”

Section: Introductionmentioning

confidence: 99%

Icos gene disruption in non‐obese diabetic mice elicits myositis associated with anti‐troponin T3 autoantibodies

Bourdenet

Pileyre

Drouot

et al. 2023

Neuropathology Appl Neurobio

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Aims: Idiopathic inflammatory myopathies (IIM) are autoimmune inflammatory disorders leading to skeletal muscle weakness and disability. The pathophysiology of IIM is poorly understood due to the scarcity of animal disease models. Genetic deletion of Icos or Icosl (inducible T cell co-stimulator/ligand) in non-obese diabetic (NOD) mice leads to muscle disease. Our aim was to characterise Icos À/À NOD myopathy and to search for novel autoantibodies (aAbs) in this model.Methods: Diabetes, weight, myopathy incidence/clinical score and grip strength were assessed over time. Locomotor activity was analysed with the Catwalk XT gait analysis system. Muscle histology was evaluated in haematoxylin/eosin and Sirius red-stained sections, and immune infiltrates were characterised by immunofluorescence and flow cytometry. 2D gel electrophoresis of muscle protein extracts and mass spectrometry were used to identify novel aAbs. NOD mice were immunised with troponin T3 (TNNT3) in incomplete Freund's adjuvant (IFA) and R848. An addressable laser bead immunoassay (ALBIA) was developed to measure aAb IgG serum levels.Results: Icos À/À NOD mice did not exhibit diabetes but developed spontaneous progressive myositis with decreased muscle strength and altered locomotor activity. Muscle from these mice exhibited myofibre necrosis, myophagocytosis, central nuclei, fibrosis and perimysial and endomysial cell infiltrates with macrophages and T cells. We identified anti-TNNT3 aAbs in diseased mice. Immunisation of NOD mice with murine TNNT3 protein led to myositis development, supporting its pathophysiological role.

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“…3 A clinical trial was conducted to study the treatment of serum-positive IMNM using complement C5 inhibitor. However, according to the latest ENMC expert report, complement inhibitors have no significant effect on targeted patients, 9 suggesting that complement activation mediated by autoantibodies may not be the key pathogenesis of serum-positive IMNM. In addition, a considerable proportion of serum-negative IMNMs have no specific autoantibodies.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune‐mediated necrotizing myopathy

Liu,

Deng,

Guo

et al. 2023

The Journal of Gene Medicine

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BackgroundImmune‐mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterized by severe proximal weakness and muscle fiber necrosis, yet its pathogenesis remains unclear. So far, there are few bioinformatics studies on underlying pathogenic genes and infiltrating immune cell profiles of IMNM. Therefore, we aimed to characterize differentially expressed genes (DEGs) and infiltrating cells in IMNM muscle biopsy specimens, which may be useful for elucidating the pathogenesis of IMNM.MethodsThree datasets (GSE39454, GSE48280 and GSE128470) of gene expression profiling related to IMNM were obtained from the Gene Expression Omnibus database. Data were normalized, and DEG analysis was performed using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using clusterProfiler. The CIBERSORT algorithm was performed to identify infiltrating cells. Machine learning algorithm and gene set enrichment analysis (GSEA) were performed to find distinctive gene signatures and the underlying signaling pathways of IMNM.ResultsDEG analysis identified upregulated and downregulated in IMNM muscle compared to the gene expression levels of other groups. GO and KEGG analysis showed that the pathogenesis of IMNM was notable for the under‐representation of pathways that were important in dermatomyositis and inclusion body myositis. Three immune cells (M2 macrophages, resting dendritic cells and resting natural killer cells) with differential infiltration and five key genes (NDUFAF7, POLR2J, CD99, ARF5 and SKAP2) in patients with IMNM were identified through the CIBERSORT and machine learning algorithm. The GSEA results revealed that the key genes were remarkably enriched in diverse immunological and muscle metabolism‐related pathways.ConclusionsWe comprehensively explored immunological landscape of IMNM, which is indicative for the research of IMNM pathogenesis.

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256th ENMC international workshop: Myositis specific and associated autoantibodies (MSA-ab): Amsterdam, The Netherlands, 8-10 October 2021

Cited by 24 publications

References 89 publications

Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis

Myxovirus resistance protein A (MxA) expression in myositides: Sarcoplasmic expression is common in both dermatomyositis and lupus myositis

Icos gene disruption in non‐obese diabetic mice elicits myositis associated with anti‐troponin T3 autoantibodies

Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune‐mediated necrotizing myopathy

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