Advances in the classification and management of idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies are a group of immune-mediated disorders characterised by multisystem involvement and a chronic disease course in two-thirds of adult patients. Autoantibodies can aid in the identification of disease subtypes and their associated severe complications, such as cancer or interstitial lung disease. Patients with idiopathic inflammatory myopathies need to be managed in a multidisciplinary setting.

Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.

Background: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people, which carry significant morbidity and mortality. Treatment of IIM represents an area of unmet need. This review is an update of a review previously published in 2012, as new and promising data on non-targeted treatments have emerged.

Targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.

Background: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people. Treatment of IIM represents an area of unmet need; a previous Cochrane review (2012) found little or no evidence to guide treatment. Since then, potentially promising treatments targeting B and T cells and complement inhibitors have been investigated.

Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioral impairment-An exploratory study.

Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease spectrum, which encompasses ALS with cognitive/behavioral impairment (ALSci/bi). In this longitudinal magnetoencephalography (MEG) study, we investigated changes in brain network topology of ALSci/bi over time as compared with ALS-pure motor and bvFTD patients. Resting-state MEG was recorded in ALS-pure motor ( = 9), ALSci/bi ( = 16), and bvFTD ( = 16) at baseline and 5-month follow-up, projected to source space.

Targeting interferon responses in juvenile dermatomyositis: Siglec-1 as an in vitro biomarker for JAK inhibitor efficacy.

Objectives: For IFN-driven diseases, such as juvenile dermatomyositis (JDM), there is a critical need for targeted therapies. We aimed to develop an in vitro model, using Siglec-1 as read-out, to evaluate inhibition of IFN-mediated responses with different JAK inhibitors (JAKi).

Methods: Healthy donor (HD) PBMCs were cultured with type I and II IFNs, TLR agonists and plasma or serum from patients (JDM, DM, JSLE, COVID-19) and HDs.

Modulating IL-21-driven B cell responses in idiopathic inflammatory myopathies via inhibition of the JAK/STAT pathway.

Background: Idiopathic inflammatory myopathies (IIM) are autoimmune disorders characterized by muscle inflammation and autoreactive B cell responses. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is essential for B cell functions, making it a promising therapeutic target. This study explores the potential of tofacitinib, a JAK1/JAK3 inhibitor, to modulate B cell activity in IIM.

Methodology Development for Investigating Pathophysiological [F]-FDG Muscle Uptake in Patients with Rheumatic Musculoskeletal Diseases.

This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [F]-FDG uptake in muscles across three different RMDs compared to controls.

Multicentre, 26-week, open-label phase 2 trial of the JAK inhibitor filgotinib in Behçet's disease, idiopathic inflammatory myopathies and IgG4-related disease: DRIMID study protocol.

Introduction: Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) faces significant challenges, including small patient populations, complex clinical trial design and difficulties in patient recruitment. Patients with Behçet's disease (BD), idiopathic inflammatory myopathies (IIM) and IgG4-related disease (IgG4-RD) typically undergo treatment involving prolonged administration of high-dose glucocorticoids and immunosuppressants. Both are associated with an increased risk of infection.

Diagnosing primary lateral sclerosis: a clinico-pathological study.

Background:  Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.

Methods: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results.

Type I interferon biomarker in idiopathic inflammatory myopathies: associations of Siglec-1 with disease activity and treatment response.

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response.

Methods: We analyzed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls.

Patient-reported daily functioning after SARS-CoV-2 vaccinations in autoimmune neuromuscular diseases.

Background And Purpose: There are concerns for safety regarding SARS-CoV-2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease-specific patient-reported outcome measures (PROMs) before and after SARS-CoV-2 vaccinations.

Methods: In this substudy of a prospective observational cohort study (Target-to-B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS-CoV-2 were included.

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group.

Background: Validated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures.

Methods: Adults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.

The impact of pain on daily activities in patients with idiopathic inflammatory myopathies: Report from the OMERACT myositis working group.

Background: International focus groups with patients with idiopathic inflammatory myopathies (IIM) conducted by the OMERACT Myositis Working Group over the years demonstrated the pain as an important symptom experienced by these patients. In this study, we aimed to examine the frequency and degree of pain interference, the aspects of daily life impacted by pain, and the factors associated with pain interference in adults with IIM.

Methods: This was a prospective observational study with two visits.

TCRβ clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity.

Objectives: To characterize the T cell receptor (TCRβ) repertoire in peripheral blood and muscle tissues of treatment naïve patients with newly diagnosed idiopathic inflammatory myopathies (IIMs).

Methods: High throughput RNA sequencing of the TCRβ chain was performed in peripheral blood and muscle tissue in twenty newly-diagnosed treatment-naïve IIM patients (9 DM, 5 NM/OM, 5 IMNM and 1 ASyS) and healthy controls. Results thereof were correlated with markers of disease activity.

Treatment with add-on IVIg in Myositis Early In the diSease course May be sUperior to Steroids alone for reaching CLinical improvEment (TIME IS MUSCLE): study protocol of a phase-2 double-blind placebo-controlled randomised trial.

Introduction: For idiopathic inflammatory myopathies (IIM) ('myositis') standard initial treatment is high-dosed glucocorticoids, which results in relatively slow improvement of muscle strength. Early immunosuppression or modulation by intensive treatment ('hit-early, hit-hard') may induce faster reduction of disease activity and prevent chronic disability due to disease-induced structural muscle damage. Intravenous immunoglobulin (IVIg) in addition to standard glucocorticoid treatment may be promising in this regard as was shown in various studies: add-on IVIg improved symptoms and muscle strength in refractory myositis patients and monotherapy IVIg improved outcomes after 9 weeks, in about half of treatment-naive patients.

Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity.

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.

Methods: IMID patients on active treatment with ISPs and controls (i.

Multimodality Screening For (Peri)Myocarditis In Newly Diagnosed Idiopathic Inflammatory Myopathies: A Cross-Sectional Study.

Background: Cardiac involvement in idiopathic inflammatory myopathy (IIM or "myositis") is associated with an approximate 4% mortality, but standardised screening strategies are lacking.

Objective: We explored a multimodality screening on potentially reversible cardiac involvement -i.e.

Disease activity in patients with immune-mediated inflammatory diseases after SARS-CoV-2 vaccinations.

For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine.

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown.

Breakthrough infections with the SARS-CoV-2 omicron (B.1.1.529) variant in patients with immune-mediated inflammatory diseases.

Objectives: To compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.

Methods: Data were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included.

Comprehensive overview of autoantibody isotype and subclass distribution.

The presence of autoreactive antibodies is a hallmark of many autoimmune diseases. The effector functions of (auto)antibodies are determined by their constant domain, which defines the antibody isotype and subclass. The most prevalent isotype in serum is IgG, which is often the only isotype used in diagnostic testing.