Publications by authors named "Iago Pinal-Fernandez"

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren's disease (SjD), and 10 healthy volunteers.

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Article Synopsis
  • This review provides an updated overview of autoimmune myopathies, focusing on risk factors, autoantibodies, and recent treatment advancements.* -
  • Recent findings show that myositis-specific autoantibodies disrupt muscle cell function, greatly impacting disease development.* -
  • Innovative treatments like CD19 CAR-T cell therapy and JAK-STAT inhibitors offer new strategies for managing myositis, while challenges with older therapies provide insights into disease mechanisms.*
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Objective: The pathogenesis of inflammatory myopathies is poorly understood and there is a need to dissect the transcriptome in more granular ways beyond gene expression.

Methods: We used a set of muscle RNA-sequencing data from different myositis subtypes grouped by their specific autoantibodies (n = 152). We quantified annotated RNA transcripts for each myositis subtype and identified uniquely expressed RNA as well as transcriptional similarities among myositis types.

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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.

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Objective: We explored the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous systemic sclerosis (dcSSc).

Methods: This phase II proof-of-concept, single center, open-label, single arm, investigator-initiated trial included patients ≥18 years, with dcSSc, modified Rodnan skin score (mRSS) ≥15 with <5 years since the first non-Raynaud's symptom and/or skin worsening despite immunosuppression who were treated with intravenous brentuximab vedotin 0.6 mg/Kg q3 weeks for 45 weeks.

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Objectives: To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM).

Methods: We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC.

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Article Synopsis
  • Myositis is an autoimmune muscle disease characterized by autoantibodies that target proteins within muscle cells, but their impact on disease development was previously unclear.* -
  • This study utilized confocal microscopy and bulk RNA sequencing on muscle biopsies to investigate the presence and effects of these autoantibodies, revealing they accumulate in muscle fibers and disrupt the normal function of their target proteins.* -
  • Findings showed that the internalization of these autoantibodies led to significant changes in gene expression and function, indicating that they play a crucial role in causing the pathology associated with myositis.*
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Introduction: Dermatomyositis (DM) is a rare inflammatory disease with diverse cutaneous and systemic manifestations, often associated with myositis-specific antibodies. Managing patients with refractory DM, or individuals presenting pecific complications, like calcinosis or rapidly progressive interstitial lung disease, presents unique challenges.

Areas Covered: This review explores current and promising treatment options for DM, drawing from clinical studies, case series, and case reports that consider the underlying disease pathophysiology.

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Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles.

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Article Synopsis
  • Immune checkpoint inhibitors (ICI) improve cancer treatment but can trigger immune-related conditions, including dermatomyositis (DM).
  • This study analyzed three DM cases linked to ICI from a patient cohort and reviewed existing literature on the topic.
  • All cases were associated with specific ICI drugs and showed a strong presence of anti-TIF1γ autoantibodies, suggesting these antibodies may contribute to developing DM in some patients.
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Objectives: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients.

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Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated.

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Article Synopsis
  • Immune-mediated necrotizing myopathy (IMNM) is an autoimmune condition causing muscle weakness and high creatine kinase levels, characterized by specific autoantibodies, with no approved treatments currently available.
  • A study named IMNM01 was conducted to evaluate the drug zilucoplan, targeting complement C5, as a potential treatment for adults with anti-HMGCR or anti-SRP positive IMNM.
  • Results showed no significant difference in muscle enzyme levels after eight weeks of treatment with zilucoplan compared to placebo, indicating that the drug did not lead to clinically meaningful improvements.
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  • Inflammatory myopathy includes various immune-mediated diseases like dermatomyositis and inclusion body myositis, with immune checkpoint inhibitors potentially causing a form known as ICI-myositis.
  • The study analyzed gene expression in muscle biopsies from various myositis patients, using bulk and single nuclei RNA sequencing techniques.
  • Results revealed three types of ICI-myositis based on gene expression profiles: ICI-DM, ICI-MYO1 (which shows high inflammation and myocarditis), and ICI-MYO2 (which has low inflammation). All subsets exhibited overexpression of genes in the IL6 pathway, with specific pathway activations noted in ICI-DM and ICI-MYO1.
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DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype, but variants in DTNA have not previously been associated with human skeletal muscle disease. We present 12 individuals from four unrelated families with two different monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin.

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Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that complement genes are locally overexpressed and correlate with markers of myositis disease activity, including the expression of interferon-gamma (IFNγ)-induced genes.

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Objective: Diagnostic muscle biopsies are routinely immunostained for major histocompatibility complex class I (MHC-I) protein. In this study we analysed the prevalence and patterns of MHC-I immunostaining in biopsies from patients with different types of myopathies and neurogenic disorders.

Methods: All 357 diagnostic muscle biopsies processed at the Johns Hopkins Neuromuscular Pathology Laboratory from August 2013 to January 2017 were immunostained for MHC-I.

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Background And Objectives: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals older than 50 years. The disorder is slowly progressive, and although many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM are limited and often conflicting.

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Purpose Of The Review: Cancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune-mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar.

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