Anti-Mi2 autoantibodies target PHD fingers of SP140L and TIF1γ, while anti-TIF1γ autoantibodies primarily bind TIF1γ outside the PHD region.

Objectives: Plant homeodomain (PHD) fingers are present in many chromatin-binding proteins. We recently discovered that anti-Mi2 autoantibodies recognize PHD fingers in Mi2 and AIRE. The purpose of this study was to characterize anti-Mi2 autoantibody recognition of PHD fingers in SP140L and TIF1γ as well as to explore recognition of TIF1γ by both anti-TIF1γ and anti-Mi2 autoantibodies.

Prevalence and functional characterization of anti-interferon autoantibodies in inflammatory myopathies.

Objectives: Functional autoantibodies targeting interferons (IFNs) can lead to immunodeficiency and have been implicated in various autoimmune diseases. Despite the critical role of interferons in myositis pathogenesis, the significance of anti-IFN autoantibodies in inflammatory myopathies remains poorly understood. This study aimed to investigate the prevalence and functional impact of anti-IFN autoantibodies in patients with myositis.

Distinct cytokine and cytokine receptor expression patterns characterize different forms of myositis.

Objective: Myositis is a heterogeneous family of inflammatory myopathies. We sought to define the differential expression of cytokines, cytokine receptors, and immune checkpoint genes in muscle biopsies from patients with different forms of myositis in order to characterize patterns of inflammation in each.

Methods: Bulk RNA sequencing was performed on muscle biopsy samples from 669 patients, including 105 with dermatomyositis, 80 with immune-mediated necrotizing myopathy (IMNM), 65 with anti-synthetase syndrome, 53 with inclusion body myositis (IBM), 19 with anti-PM/Scl myositis, 310 with other inflammatory or genetic myopathies, and 37 controls with normal tissue (NT).

Identification of a distinctive gene signature in granulomatous myositis.

Objectives: Granulomatous myositis (GM) is defined by focal collections of activated macrophages that fuse to form multinucleated cells that aggregate into granulomas within skeletal muscle. This study aimed to elucidate the pathophysiology of GM by defining its specific transcriptomic profile.

Methods: Bulk RNA sequencing was performed on 722 muscle biopsies, including 38 from patients with GM, other myopathies, and healthy comparators.

Anti-Mi2 autoantibodies target the PHD fingers of SP140L and TIF1γ, while anti-TIF1γ autoantibodies primarily recognize epitopes outside the PHD region of TIF1γ.

Objectives: Plant homeodomain (PHD) fingers are present in many chromatin-binding proteins. We recently discovered that anti-Mi2 autoantibodies recognize PHD fingers in Mi2 and AIRE. The purpose of this study was to characterize anti-Mi2 autoantibody recognition of PHD fingers in SP140L and TIF1γ as well as to explore recognition of TIF1γ by both anti-TIF1γ and anti-Mi2 autoantibodies.

Myositis-specific autoantibodies recognizing Mi2 also target the autoimmune regulator (AIRE) protein at a shared PHD-zinc finger.

Objectives: In dermatomyositis patients with anti-Mi2 autoantibodies, autoantibodies can enter muscle cells, leading to the aberrant expression of genes normally repressed by the Mi2/nucleosome remodeling and deacetylation (NuRD) complex. However, the mechanism by which autoantibodies interfere with Mi2/NuRD function remains unclear. This study aimed to identify additional autoantibodies in anti-Mi2-positive patients as well as the specific epitopes recognized by anti-Mi2 and any novel autoantibodies.

Eosinophilic fasciitis.

Eosinophilic fasciitis is a rare scleroderma-like syndrome of unknown cause. It is characterized by painful induration and progressive thickening of the muscular fascia and subcutaneous tissue of the limbs and trunk. The most common laboratory findings include peripheral eosinophilia, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate.

Activated Dendritic Cell Subsets Characterize Muscle of Inclusion Body Myositis Patients and Correlate with KLRG1+ and TBX21+ CD8+ T cells.

Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterized by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells and type 1 inflammation. Myeloid dendritic cells (mDCs), including type 1 conventional dendritic (cDC1) cells, type 2 conventional dendritic (cDC2) cells, and mature immunoregulatory dendritic (mregDC) cells, have previously been reported in skeletal muscle of IBM patients and may activate these cytotoxic T cells. Here, we analyzed single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (RNA-seq) data from skeletal muscle of IBM, other myositis, and control patients to identify and quantify these mDC subsets and characterize their contribution to IBM inflammation.

Local immunoglobulin expression in myositis is associated with interferon gamma signaling and correlates with disease activity.

Objectives: Autoantibodies may play a role in the pathogenesis of myositis and are locally produced within muscle tissue. This study aimed to characterize the local expression of immunoglobulin genes across different subgroups of myositis, identify pathways associated with this expression, and evaluate correlations with disease activity.

Methods: Bulk RNA sequencing was performed on muscle biopsies from 289 individuals, including patients with various forms of myositis and healthy controls.

Consensus nomenclature and abbreviation for anti-synthetase syndrome: an IMACS project.

Objectives: The lack of uniform terminology and abbreviations for anti-synthetase syndrome has led to significant challenges in research and clinical practice. This study aimed to establish an international consensus on a standardized nomenclature and abbreviation among a diverse group of global myositis experts and patient representatives.

Methods: This qualitative project was approved by the International Myositis Assessment and Clinical Studies Group (IMACS).

Treatment and Monitoring of Eosinophilic Fasciitis.

Purpose Of Review: Eosinophilic fasciitis (EF) is a rare inflammatory disease characterized by skin induration. Although some guidelines from scientific societies exist, standard recommendations on monitoring and therapy are lacking.

Recent Findings: Current therapy for patients diagnosed with EF includes glucocorticoids plus at least one immunosuppressive drug in cases of relapse or refractory disease.

The role of multicriteria decision analysis in the development of candidate classification criteria for antisynthetase syndrome: analysis from the CLASS project.

Objectives: To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD).

Methods: A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD.

Distinct Cytokine and Cytokine Receptor Expression Patterns Characterize Different Forms of Myositis.

Objective: Myositis is a heterogeneous family of inflammatory myopathies. We sought to define the differential expression of cytokines, cytokine receptors, and immune checkpoint genes in muscle biopsies from patients with different forms of myositis in order to characterize patterns of inflammation in each.

Methods: Bulk RNA sequencing was performed on muscle biopsy samples from 669 patients, including 105 with dermatomyositis, 80 with immune-mediated necrotizing myopathy (IMNM), 65 with anti-synthetase syndrome, 53 with inclusion body myositis (IBM), 19 with anti-PM/Scl myositis, 310 with other inflammatory or genetic myopathies, and 37 controls with normal tissue (NT).

Human induced pluripotent stem cell-derived myotubes to model inclusion body myositis.

Inclusion body myositis (IBM) is an inflammatory myopathy that displays proximal and distal muscle weakness. At the histopathological level, the muscles of IBM patients show inflammatory infiltrates, rimmed vacuoles and mitochondrial changes. The etiology of IBM remains unknown, and there is a lack of validated disease models, biomarkers and effective treatments.

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

Objective: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

Pathological autoantibody internalisation in myositis.

Objectives: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption.