OBJECTIVE: To determine the prevalence, distribution, and clinical manifestations of arthritis in a cohort of patients with idiopathic inflammatory myopathies (IIM). Associations with autoantibody status and HLA genetic background were also explored. METHODS: Consecutive patients with IIM treated in a single center were included in this cross-sectional study (n = 106). History of arthritis, 68-joint and 66-joint tender and swollen joint index, clinical features of IIM, and autoantibody profiles were obtained by clinical examination, personal interview, and review of patient records. High-resolution genotyping in HLA-DRB1 and HLA-DQB1 loci was performed in 71 and 73 patients, respectively. RESULTS: A combination of patients' medical history and cross-sectional physical examination revealed that arthritis at any time during the disease course had occurred in 56 patients (53%). It was present at the beginning of the disease in 39 patients (37%) including 23 cases (22%) with arthritis preceding the onset of muscle weakness. On physical examination, 29% of patients had at least 1 swollen joint. The most frequently affected areas were wrists, and metacarpophalangeal and proximal interphalangeal joints. Twenty-seven out of the 29 anti-Jo1-positive patients had arthritis at any time during the course of their illness; this prevalence was significantly higher compared to patients without the anti-Jo1 autoantibody (p < 0.0001). No association of arthritis with individual HLA alleles was found. CONCLUSION: Our data suggest that arthritis is a common feature of myositis. It is frequently present at the onset of disease and it may even precede muscular manifestations of IIM. The most common presentation is a symmetrical, nonerosive polyarthritis affecting particularly the wrists, shoulders, and small joints of the hands. We have confirmed a strong association of arthritis with the presence of the anti-Jo1 antibody.

• Klíčová slova
• ARTHRITIS, AUTOANTIBODIES, IDIOPATHIC INFLAMMATORY MYOPATHIES,
• MeSH
• alely MeSH
• artritida epidemiologie   genetika   imunologie   MeSH
• autoprotilátky * MeSH
• dospělí MeSH
• genotyp MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida epidemiologie   genetika   imunologie   MeSH
• prevalence MeSH
• průřezové studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky * MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQB1 antigen MeSH Prohlížeč
• HLA-DRB1 řetězec MeSH

BACKGROUND: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis. OBJECTIVES: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients. METHODS: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes. RESULTS: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009). CONCLUSIONS: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies.

• Klíčová slova
• Disease activity, IL-35, Idiopathic inflammatory myopathy, Muscle biopsy,
• MeSH
• biopsie MeSH
• dítě MeSH
• dospělí MeSH
• interleukiny krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myozitida krev   metabolismus   patologie   MeSH
• polymyozitida krev   metabolismus   patologie   MeSH
• senioři MeSH
• svaly metabolismus   patologie   MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-35, human MeSH Prohlížeč
• interleukiny MeSH

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that these are systemic inflammatory disorders. Different myositis-specific autoantibodies have been identified and, on the basis of clinical, histopathological and serological features, IIMs can be classified into several subgroups — dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the autoantigens of the immune reactions in these subgroups is crucial to improve outcomes. New, more homogeneous subgroups defined by autoantibodies may help define disease mechanisms, and will also be important in future clinical trials to develop targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

• MeSH
• lidé MeSH
• myozitida * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: Arthritis is a well-recognized symptom of idiopathic inflammatory myopathies (IIM). We provide a summary of available data regarding the epidemiology, clinical characteristics, and autoantibody associations of joint involvement in various forms of IIM. RECENT FINDINGS: Arthritis is reported in 18-55% of patients with IIM. It is particularly frequent (20-70%) in those with antisynthetase syndrome (ASS); highest prevalence is associated with anti-Jo-1 positivity. Most common manifestation is non-erosive polyarthritis. X-ray erosions may be found occasionally in ASS, particularly in patients with overlap with rheumatoid arthritis (RA). Arthritis is often present at the time of IIM diagnosis and it may even precede the onset of muscle weakness. Arthritis may in some cases be the main disease manifestation responsible for the disease burden in patients with IIM. Arthritis is a frequent symptom of IIM. Polyarthritis of small joints of the hands is the most frequent clinical manifestation. Arthritis may be the first or dominant symptom in IIM and therefore patients may be initially misdiagnosed as having RA. Particularly in seronegative RA patients with interstitial lung disease or Raynaud's phenomenon, the possibility of IIM should be considered.

• Klíčová slova
• Anti-Jo-1, Antisynthetase syndrome, Arthritis, Floppy-thumb, Idiopathic inflammatory myopathies,
• MeSH
• artritida diagnóza   epidemiologie   MeSH
• lidé MeSH
• myozitida komplikace   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

• MeSH
• autoimunitní nemoci * diagnóza   MeSH
• autoprotilátky MeSH
• dermatomyozitida * patologie   terapie   MeSH
• lidé MeSH
• myozitida s inkluzními tělísky * patologie   MeSH
• myozitida * diagnóza   patologie   MeSH
• svalová slabost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• autoprotilátky MeSH

KEY POINTS: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls. A 6-month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids. These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. ABSTRACT: Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease-related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6-month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index-matched controls. [14 C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 μm). Reduced oxidative (intermediate metabolites, -49%, P = 0.034) and non-oxidative (diglycerides, -38%, P = 0.013) lipid metabolism was identified in palmitate-treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2 , P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate-induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non-immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6-month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms.

• Klíčová slova
• exercise, human skeletal muscle cells, idiopathic inflammatory myopathy, lipid metabolism, mitochondria,
• MeSH
• kosterní svalová vlákna metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• kvalita života MeSH
• lidé MeSH
• metabolismus lipidů * MeSH
• myozitida * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Major advances have been made in the field of idiopathic inflammatory myopathies (IIM), or myositis, that are likely to facilitate development of new therapeutic strategies that have not yet been applied in this group of diseases. These advances include new classification criteria to better identify the patients with IIM, detection of several new myositis-specific autoantibodies that facilitates subgrouping of patients into more specific clinical phenotypes, development of outcome measures for disease activity, and new response criteria. We have learned from clinical studies that exercise is an important part of treatment and that pharmacologic treatment should be combined with exercise.

• Klíčová slova
• Autoantibodies, Criteria, Exercise, Myositis, Target, Treatment,
• MeSH
• antirevmatika farmakologie   MeSH
• autoprotilátky analýza   MeSH
• lidé MeSH
• management péče o pacienta metody   MeSH
• myozitida * diagnóza   imunologie   terapie   MeSH
• stupeň závažnosti nemoci MeSH
• určení symptomu metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antirevmatika MeSH
• autoprotilátky MeSH

BACKGROUND: In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM. METHODS: We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules. FINDINGS: We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl, -Mi2, -Jo1, -Jo1/Ro52, -TIF1γ or negative for all analysed autoantibodies. Associations with HLA-DRB1∗11, HLA-DRB1∗15, HLA-DQA1∗03, and HLA-DQB1∗03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1∗03, HLA-DQA1∗05, and HLA-DQB1∗02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/Ro52-dominated subgroups. HLA-DRB1∗16, HLA-DRB1∗07 alleles were most frequent in anti-Mi2 and HLA-DRB1∗01 and HLA-DRB1∗07 alleles in the anti-TIF1γ subgroup. The HLA-DRB1∗13, HLA-DQA1∗01 and HLA-DQB1∗06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1γ, and the negative subgroup. INTERPRETATION: Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

• Klíčová slova
• Autoantibody, HLA, Idiopathic inflammatory myopathy, Myositis,
• MeSH
• alely MeSH
• autoprotilátky * genetika   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé MeSH
• myozitida * genetika   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky * MeSH
• HLA-DRB1 řetězec MeSH

INTRODUCTION: The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. METHODS: Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. RESULTS: In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. CONCLUSIONS: The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.

• MeSH
• imunohistochemie MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida krev   imunologie   patologie   MeSH
• resistin krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• resistin MeSH

OBJECTIVE: The interplay between dysphagia, cancer, and mortality in idiopathic inflammatory myopathies (IIM) has not been carefully studied. The aim of this study was to investigate possible effect modification of cancer on the association between dysphagia and mortality in early IIM. METHODS: A multi-center cohort of 230 adult IIM patients with dysphagia assessment within 6 months of disease onset was assembled. Crude mortality rates in IIM patients exposed or not to dysphagia were estimated for the 5-year period following cohort entry. To explore possible effect modification of cancer on the association between dysphagia and mortality, adjusted Cox models stratified on cancer status were performed as well as an interaction model. RESULTS: Mortality rates per 100 person-years for IIM patients exposed to dysphagia were 2.3 (95 %CI 1.0 to 4.5) in those without cancer compared to 33.3 (95 %CI 16.6 to 59.5) in those with cancer. In stratified Cox models, the main effect of dysphagia was HR 0.5 (95 %CI 0.2 to 1.5) in non-cancer and 3.1 (95 %CI 1.0 to 10.2) in cancer patients. In the interaction model, the combination of dysphagia and cancer yielded a HR of 6.4 (1.2 to 35.1). CONCLUSION: In this IIM cohort, dysphagia in non-cancer patients was not associated with increased mortality, while it was in presence of cancer, supporting effect modification of cancer on the association between dysphagia and mortality. This suggests that IIM patients with and without cancer differ and separate analyses for the two groups should be conducted when the outcome of interest is mortality.

• Klíčová slova
• Cancer, Dysphagia, Idiopathic inflammatory myopathy, Mortality,
• MeSH
• dospělí MeSH
• lidé MeSH
• myozitida * komplikace   MeSH
• nádory * komplikace   MeSH
• poruchy polykání * komplikace   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH