Search Results (118)

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with wide variation in pathogenesis, clinical presentation, and serological profiles, leading to substantial differences in diagnosis, classification, treatment response, and prognosis among patients. Although decades of progress have been made in understanding myositis-specific autoantibodies and molecular pathology, important gaps remain in elucidating disease mechanisms and identifying effective therapeutic targets. Therefore, animal models that recapitulate key characteristics of human IIMs provide an indispensable platform for addressing current limitations in mechanistic research and promoting translational studies. This review comprehensively discusses animal models related to the major clinical–serological subtypes of IIMs, including polymyositis-like T-cell-mediated models, dermatomyositis models, inclusion body myositis models, antisynthetase syndrome models, and immune-mediated necrotizing myopathy models. Particular attention is given to model construction, pathological phenotypes, dominant immune mechanisms, therapeutic applications, and translational limitations. By organizing current models according to subtype-related pathological and immunological features, this narrative review aims to provide a clearer framework for selecting appropriate experimental systems and to facilitate more precise, mechanism-driven myositis research. Full article

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Background: Neutrophils play a role in idiopathic inflammatory myopathies (IIMs), especially in vasculopathic manifestations. While neutrophil extracellular traps (NETs) and low-density granulocytes (LDGs) have been described, the functional relevance of other subsets—such as naïve neutrophils, reverse transendothelial migration neutrophils (rTEM), myeloid-derived suppressor cells (MDSCs), and regulatory neutrophils—and their association with vasculopathy remains unknown. Objective: We aimed to characterize the phenotypic and functional profile of neutrophil subsets and their association with vasculopathic manifestations in IIM, adjusting for disease activity. Methods: We conducted a cross-sectional, single-center study including 59 IIM patients diagnosed by muscle biopsy and fulfilling 2017 ACR/EULAR criteria. Flow cytometry was used to immunophenotype myeloid subsets, and functional assays assessed phagocytosis and respiratory burst. Patients were stratified by clinical activity and presence of vasculopathy. Results: Vasculopathic patients showed expansion of LDGs (p = 0.0092), granulocytic and monocytic MDSCs expressing Arginase-1 (p = 0.0078, p = 0.0003) and PD-L1 (p = 0.0258, p = 0.0087), and rTEM neutrophils (p = 0.0775). In contrast, they exhibited a reduction in naïve neutrophils (p = 0.0004), phagocytosis (p < 0.0001) and respiratory burst (p = 0.0006). Multivariate analysis identified naïve neutrophils and activated CD177⁺ neutrophils as independent predictors of vasculopathy. A positive correlation between activated and naïve neutrophils were observed in patients with vasculopathic features (r = 0.43; p < 0.05). Conclusions: IIM patients with vasculopathic features display a distinct immune profile characterized by an imbalance between proinflammatory and regulatory neutrophil subsets, alongside persistent functional impairment. Full article

Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with the goal of advancing personalized medicine. Methods: A computer-assisted search was conducted to identify patients with a diagnosis of IIM seen at Attikon University Hospital, from January 2010 to December 2025. Medical records were reviewed for clinical, laboratory and serological features. Results: We identified 140 patients with IIM; 96 (68.6%) were female with a mean age at diagnosis of 55.8 years (SD 15.7). ILD was present in 75 patients (53.6%), being more common among males (30/44, 68.2% vs. 45/96 females, 46.9%, p = 0.019). Patients in the ILD subgroup were older at diagnosis (mean age 60.2 years vs. 50.7 years, p < 0.001) and presented more often with dyspnea (41 vs. 1, p < 0.001), higher CRP (median 5.95 mg/L vs. 2.9 mg/L, p = 0.024), and lower CPK (median 103 vs. 580, p < 0.001). Patients first seen by a pulmonologist were more likely to be older (mean age 60.5 years vs. 53 years, p = 0.002) and to present with dyspnea (33 vs. 9, p < 0.001) and ILD (48 vs. 27, p < 0.001). By contrast, skin involvement (61% vs. 27%, p = 0.04), muscle weakness (53 vs. 15, p < 0.001) and elevated CPK (median 301.5 vs. 103.5, p = 0.013) were less frequent in these patients as compared to patients first evaluated by a rheumatologist. Anti-tRNA synthetase, anti-Ro52 and anti-Pm/Scl antibodies were more frequent in the ILD subgroup. Anti-tRNA antibodies were also more frequent in patients first seen by a pulmonologist. Conclusions: Patients with IIM-ILD are more likely to present without overt clinical or biochemical characteristics of muscle involvement, thereby increasing the likelihood of initial evaluation by pulmonologists. Full article

Background/Objectives: We report a case of severe dermatomyositis demonstrating characteristic widespread extraosseous uptake on ^99mTc-methylene diphosphonate (^99mTc-MDP) bone scintigraphy. This study highlights the diagnostic value of this modality in detecting active inflammatory myopathy when conventional muscle biopsy is inconclusive and introduces its novel use for intraoperative gamma-probe-guided biopsy to precisely target metabolically active muscle. This approach may help target metabolically active muscle in heterogeneous idiopathic inflammatory myopathies (IIMs). Case Presentation: A 49-year-old man developed progressive proximal muscle weakness (Medical Research Council grade 2/5 proximally, 5/5 distally) beginning in June 2025 following influenza infection, accompanied by dysphagia, classic dermatomyositis cutaneous manifestations, back pain, and difficulty standing. Laboratory evaluation revealed elevated inflammatory markers (ESR 55 mm/hr, CRP 20 mg/L), leukocytosis (16.58 × 10⁹/L), markedly raised creatine kinase (19,937 IU/L), and troponin T levels. An initial quadriceps muscle biopsy performed on 29 July 2025 was non-diagnostic. Three-phase ^99mTc-MDP scintigraphy (~1110 MBq) demonstrated intense, diffuse extraosseous uptake involving bilateral deltoids (symmetric), biceps and triceps (patchy), paraspinal muscles (longitudinal), gluteal muscles, thighs (quadriceps and hamstrings), and gastrocnemius muscles, with relative suppression of appendicular skeletal uptake on delayed images due to soft-tissue tracer dominance—findings consistent with severe inflammatory myopathy. Following reinjection (~1100 MBq), intraoperative gamma-probe-guided biopsy targeted areas of highest uptake (left quadriceps femoris and distal triceps brachii; intraoperative counts 1300–1400 versus background ~500). Histopathology revealed histiocyte-predominant inflammation with myofibre necrosis and regeneration, sparse CD4⁺ T-cell infiltrates, and absence of fibrosis, consistent with necrotising myopathy. Positive antinuclear antibodies and strong anti-Mi-2 antibodies confirmed the diagnosis of dermatomyositis. Treatment included pulse methylprednisolone followed by oral prednisone taper, methotrexate, azathioprine, intravenous immunoglobulin, and planned rituximab therapy. Discussion: Whole-body ^99mTc-MDP scintigraphy provided a complementary whole-body functional assessment of disease extent, revealing widespread muscular involvement. The novel application of intraoperative gamma-probe-guided biopsy enabled real-time targeting of metabolically active muscle, facilitating targeted sampling after an initial non-diagnostic biopsy and yielding supportive histopathological findings. This dual diagnostic and interventional role demonstrates the technical feasibility of gamma-probe guidance in a diagnostically challenging case of dermatomyositis. Conclusions: In our case, the integration of ^99mTc-MDP scintigraphy with gamma-probe-guided biopsy enabled precise targeting of metabolically active muscle following an initial non-diagnostic biopsy. This multimodal approach may be useful in selected diagnostically challenging cases of severe inflammatory myopathy. Larger studies are needed to evaluate its reproducibility and added value. Full article

The prostaglandin D2 receptor (PTGDR) -441 C/T polymorphism has been previously associated with inflammatory diseases such as asthma. The goal of this study was to explore the association of this polymorphism with idiopathic inflammatory myopathies (IIM) and their clinical features. Seventy-two healthy subjects (HS) and forty-eight patients with IIM from Guadalajara and Mexico were recruited over three years. Clinical features and enzymes used for diagnostics and follow-up, such as creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate transaminase (AST), and alanine aminotransferase (ALT), were collected at the recruitment point and from the chart at the diagnostic point. PCR-ARMS was used to define genotypes. The Chi-square test was used to compare genotype and allele frequencies and clinical features between IIM patients and healthy subjects. A one-way ANOVA on ranks was performed to compare enzymatic levels. The allele distribution was not in Hardy–Weinberg equilibrium in the controls. There was no difference in age or gender distribution between the groups. The polymorphic (T) allele was more common in the IIM group than in the HS group. At the same time, the wild-type (CC) genotype presented more clinical features, such as heliotrope rash, fever, dyspnea, and weight loss, than the TT genotype. No significant differences were found regarding the enzyme levels. To further understand the role of this polymorphism in IIM, a bigger sample size is required along with mechanistical studies. Nevertheless, the polymorphic allele of the PTGDR -441 C/T polymorphism suggests susceptibility to IIM, whereas the wild-type CC genotype is associated with more clinical features. Full article

Objectives: The genetic architecture of B-cell lymphomas is not fully characterized. We aimed to identify novel candidate variants associated with four common B-cell lymphoma subtypes—diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL)—through cross-trait analyses with correlated idiopathic inflammatory myopathies subtypes, dermatomyositis (DM) and polymyositis (PM). Methods: Leveraging shared genetic susceptibility with DM and PM, we applied a pleiotropy-informed conditional false discovery rate (condFDR) method to recompute nominal single nucleotide polymorphism association p-values for each B-cell lymphoma subtype. Associations were considered significant at condFDR <0.01. Functional annotation was performed using FUMA (Functional Mapping and Annotation of Genome-Wide Association Studies), followed by Gene Ontology (GO) enrichment analysis via clusterProfiler, with similar GO terms clustered for interpretation and visualization. Results: We identified 4, 2, 13, and 6 novel candidate loci for DLBCL, FL, CLL, and MZL, respectively. Most loci exhibited regulatory effects on genes involved in adaptive immune responses and cell death pathways. Notably, for DLBCL locus 1q23.3 affects SLAMF genes implicated in natural killer and lymphocyte activation. A trans-eQTL at 2q13 for FL was associated with BCL11A, a multifunctional oncogene. For CLL, a novel locus at 16q24.1 regulates IRF8, a known CLL risk gene. Functional mapping of previously reported CLL risk loci revealed RIPK1 (6p25.2), linked to necroptosis. No enriched biological pathways were detected for MZL risk-associated genes. Conclusions: These findings advance our understanding of the genetic architecture of four B-cell lymphoma subtypes and aim to inform future genetic and functional studies. Full article

Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m². The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research. Full article

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are critical biomarkers in myositis, associated with distinct clinical features and prognosis. This study aimed to evaluate the proportion of anti-MDA5 positivity and compare the diagnostic performance of local immunoblotting (IB) with gold-standard immunoprecipitation (IP). We performed a retrospective analysis of 3272 physician-requested anti-MDA5 IB determinations over a five-year period (2019–2023). A subsequent exploratory pilot study of ten Hungarian patients with myositis was conducted to compare IB results with radiolabeled protein IP. Confirmatory in-house enzyme-linked immunosorbent assay (ELISA) was used to distinguish between 140 kDa bands (anti-MDA5 vs. anti-NXP2). Indirect immunofluorescence (IIF) on HEp-2 cells was also evaluated. In the retrospective cohort, 3.7% (n = 121) of samples were non-negative. Among 64 borderline patients, only one (1.6%) had a definitive diagnosis of dermatomyositis (DM). Conversely, the proportion of confirmed myositis cases was notably higher among patients with strong positive IB results. In our exploratory cross-sectional pilot study, complete concordance between the two assays was observed for negative and strong positive results. Discrepancies were noted in borderline and weak positivity ranges, where anti-MDA5 was not detected by IP; instead, alternative autoantibodies were identified. The three IP-confirmed MDA5 positive samples were all validated by ELISA. The characteristic IIF cytoplasmic staining was identifiable in 2 out of 10 cases (20%). In our cohort, borderline IB cases were frequently potential false positives, highlighting the need for careful clinical evaluation. Borderline and weak results require clinical correlation or confirmatory testing to avoid misdiagnosis. Full article

Idiopathic inflammatory myopathies constitute a group of immune-mediated disorders primarily affecting skeletal muscle, but they may also lead to significant involvement of internal organs. These conditions are highly heterogeneous, encompassing diverse clinical manifestations and multiple underlying pathophysiological mechanisms. A unifying feature across this disease spectrum is an autoimmune response characterized by the production of highly specific autoantibodies, which are detected in the majority of patients. Genetic studies have identified the principal susceptibility background as the 8.1 ancestral haplotype within the HLA region on chromosome 6. However, genetic predisposition extends beyond HLA loci and includes numerous genes encoding key molecules involved in cytokine production, the regulation of immune signaling pathways, and metabolic processes. In this paper, we review the currently identified genetic loci associated with inflammatory myopathies, with particular emphasis on the HLA system, as well as non-HLA genes and newly identified candidates. Full article

Skeletal muscle is vital for movement and metabolism, and its dysfunction underpins disorders like muscular dystrophy and sarcopenia, severely impacting life quality. In these diseases, various cell death pathways are pivotal, driving core pathological features such as fiber loss and chronic inflammation. This study reviews the central role of cell death in skeletal muscle diseases, and analyzes its roles and mechanisms in genetic muscle disorders such as Duchenne muscular dystrophy (DMD), glycogen storage diseases (GSD), mitochondrial myopathies, as well as acquired muscle disorders such as idiopathic inflammatory myopathy, sarcopenia, rhabdomyolysis, and myasthenia gravis (MG). We also explore the potential of cell death-related molecules as biomarkers and discuss emerging therapeutic strategies that target these pathways, aiming to provide new insights for diagnosis and treatment. Full article

Background: Idiopathic inflammatory myopathies (IIMs), characterized by muscle weakness and chronic inflammation, currently lack highly effective therapies. This study investigated the therapeutic potential and underlying mechanism of (5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with reduced toxicity, using an experimental autoimmune myositis (EAM) mouse model and in vitro assays. Methods: Forty female BALB/c mice were randomly assigned to five groups: normal, vehicle, methylprednisolone (MP), LLDT-8 (0.0625 mg/kg), and LLDT-8 (0.125 mg/kg). EAM mice were treated with LLDT-8 (0.0625 or 0.125 mg/kg) or methylprednisolone as a positive control. Cellular experiments and molecular docking were performed to investigate potential mechanisms of LLDT-8. Results: LLDT-8 significantly attenuated clinicopathological features, including muscle weakness and pain sensitivity, while reducing serum levels of aspartate aminotransferase and lactate dehydrogenase. Histological analysis revealed that LLDT-8 reduced inflammatory cell infiltration and the presence of CD4⁺ and CD8⁺ T cells in muscle tissues. Mechanistically, LLDT-8 inhibited the expression of nucleotide-binding oligomerization domain receptor caspase recruitment domain 5 (NLRC5), a key transcriptional regulator of major histocompatibility complex-I (MHC-I). This suppression extended to downstream antigen presentation-related molecules, including the transporter associated with antigen processing and proteasome 20S subunit beta. Molecular docking further confirmed the high binding affinity of LLDT-8 to both NLRC5 and MHC-I. Conclusions: LLDT-8 alleviates inflammatory muscle injury by targeting the NLRC5/MHC-I signaling axis, suggesting it may be a promising therapeutic candidate for IIMs. Full article

Dermatomyositis (DM) is a rare, autoimmune inflammatory myopathy characterized by a heterogeneous clinical course and complex etiopathogenesis. Although classically defined by the coexistence of muscle inflammation and distinctive skin lesions, DM frequently presents as a systemic disease, and, in some patients, cutaneous manifestations may precede muscle involvement or represent the sole clinical feature. The spectrum of skin lesions in DM is broad and includes pathognomonic, characteristic, rare, or atypical manifestations, ranging from classic Gottron’s sign and heliotrope rash to uncommon subtypes such as vesiculobullous dermatomyositis, Wong-type dermatomyositis, or flagellate dermatitis. Particular cutaneous phenotypes often correlate with distinct clinical subtypes, autoantibody profiles, systemic involvement, and prognosis. The diversity of dermatological presentations and their resemblance to other dermatoses may delay accurate diagnosis, especially in amyopathic and hypomyopathic forms of the disease. The aim of this review is to comprehensively discuss the wide spectrum of cutaneous manifestations of dermatomyositis, emphasize less recognized and rare dermatological clinical presentations, and highlight their diagnostic and prognostic significance. However, histopathological examination may support the diagnostic process in challenging cases. Early identification of characteristic skin lesions remains crucial for prompt diagnosis, appropriate screening for systemic complications and malignancy, and optimal management. Close interdisciplinary cooperation among dermatologists, rheumatologists, and other specialists is essential to ensure accurate diagnosis and improve outcomes in patients with dermatomyositis. Full article

Muscle biopsy (MB) is an important tool to help differentiate idiopathic inflammatory myopathies (IIMs) from hereditary muscular diseases (HMDs). The usefulness of immunohistochemical stains of the major histocompatibility complex class I and the membrane attack complex are controversial, as both may be identified in some HMDs. More sensitive markers of IIMs have recently been used, such as myxovirus resistance A (MxA), a type I interferon-inducible protein. We selected skeletal MB samples from 81 patients diagnosed with IIM and HMD harbouring overt inflammatory infiltrates on their MBs in the period between March 2022 and September 2024. Two groups were identified: the IIM group (46 cases) and the HMD group (35 cases). We characterized and compared the patterns of MxA protein expression among the two groups. In the IIM group, positive sarcoplasmic MxA expression was detected on the myofibres of 10 patients (24%), among whom were eight dermatomyositis patients. In the HMD group, we did not identify any sarcoplasmic positivity. However, five patients (14%) showed positive labelling restricted to the sarcolemmal membrane, including non-necrotic or regenerating fibres. Our study demonstrates the value of MxA for increasing dermatomyositis diagnostic accuracy and suggests the potential role of interferon type I in the pathophysiology of HMD. Full article

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24–81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10–240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts. Full article