Autoimunní revmatická onemocnění jsou rozmanitou skupinou stavů, které se mohou projevovat tvorbou autoprotilátek, funkčními poruchami imunity a systémovými projevy. Diagnostika může být obtížná kvůli mnoha nespecifickým projevům. Klíčovým testem, který v praxi využíváme, je stanovení orgánově nespecifických autoprotilátek. Autoprotilátky vyskytující se u osob se systémovými revmatickými chorobami mohou sloužit nejen jako markery pro klasifikaci, diagnózu a prognózu onemocnění, ale také při hodnocení aktivity onemocnění a při rozhodování o léčebném postupu. Autoprotilátky také často hrají přímou úlohu v patogenezi jednotlivých onemocnění.

Autoimmune rheumatic diseases represent a diverse group of conditions that may manifest with the production of autoantibodies, immune dysfunction, and systemic symptoms. Diagnosis can be challenging due to many nonspecific manifestations. A key test used in practice is the detection of organ-nonspecific autoantibodies. Autoantibodies present in individuals with systemic rheumatic diseases can serve not only as markers for classification, diagnosis, and prognosis but also in assessing disease activity and guiding treatment decisions. Autoantibodies often also play a direct role in the pathogenesis of individual diseases.

• MeSH
• Antigens, Nuclear immunology   MeSH
• Antibodies, Antinuclear immunology   MeSH
• Autoimmune Diseases diagnosis   immunology   MeSH
• Autoantibodies * immunology   classification   MeSH
• Immunologic Techniques methods   MeSH
• Humans MeSH
• Myositis immunology   MeSH
• Antibodies, Antineutrophil Cytoplasmic immunology   MeSH
• Antibodies immunology   classification   MeSH
• Rheumatic Diseases * diagnosis   immunology   MeSH
• Rheumatoid Factor immunology   MeSH
• Scleroderma, Systemic immunology   MeSH
• Lupus Erythematosus, Systemic diagnosis   immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

• MeSH
• Autoantibodies * blood   immunology   MeSH
• Dermatomyositis immunology   blood   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Myositis * immunology   blood   MeSH
• Disease Progression MeSH
• Registries * MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). RESULTS: In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes-heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)-differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

• MeSH
• Amino Acyl-tRNA Synthetases immunology   MeSH
• Autoantibodies * blood   immunology   MeSH
• Dermatomyositis * immunology   complications   MeSH
• Adult MeSH
• Exanthema etiology   MeSH
• Lung Diseases, Interstitial immunology   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Myositis * immunology   complications   MeSH
• Neoplasms complications   MeSH
• Registries * MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Genome-wide association studies (GWASs) have been successful at finding associations between genetic variants and human traits, including the immune-mediated diseases (IMDs). However, the requirement of large sample sizes for discovery poses a challenge for learning about less common diseases, where increasing volunteer numbers might not be feasible. An example of this is myositis (or idiopathic inflammatory myopathies [IIM]s), a group of rare, heterogeneous autoimmune diseases affecting skeletal muscle and other organs, severely impairing life quality. Here, we applied a feature engineering method to borrow information from larger IMD GWASs to find new genetic associations with IIM and its subgroups. Combining this approach with two clustering methods, we found 17 IMDs genetically close to IIM, including some common comorbid conditions, such as systemic sclerosis and Sjögren's syndrome, as well as hypo- and hyperthyroidism. All IIM subtypes were genetically similar within this framework. Next, we colocalized IIM signals that overlapped IMD signals, and found seven potentially novel myositis associations mapped to immune-related genes, including BLK, IRF5/TNPO3, and ITK/HAVCR2, implicating a role for both B and T cells in IIM. This work proposes a new paradigm of genetic discovery in rarer diseases by leveraging information from more common IMD, and can be expanded to other conditions and traits beyond IMD.

• MeSH
• Autoimmune Diseases genetics   immunology   MeSH
• Genome-Wide Association Study * MeSH
• Genetic Predisposition to Disease * MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Myositis * genetics   immunology   MeSH
• Immune System Diseases genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Revmatologie zažívá v posledních letech významný pokrok, který je důsledkem zdůrazňování časné diagnostiky a uplatňo- vání principů léčby k cíli, stejně jako nových imunopatogenetických poznatků a dostupnosti širokého spektra biologických a cílených syntetických léčivých přípravků. V tomto sdělení přinášíme nové poznatky z oblasti diagnostiky a léčby vybraných revmatických onemocnění, a to konkrétně revmatoidní artritidy, spondyloartritid, systémového lupus erythematodes, systémové sklerodermie, idiopatických zánětlivých myopatií, systémových vaskulitid, revmatické polymyalgie a obrov- skobuněčné arteriiitidy a také osteoartrózy. Toto sdělení si klade za cíl přinést souhrn nejnovějších poznatků a trendů v diagnostice a léčbě těchto revmatických onemocnění, které mají zásadní vliv na kvalitu života pacientů.

Rheumatology has experienced significant advances in recent years as a result of the emphasis on early diagnosis and the application of treat-to-target principles, as well as new immunopathogenetic findings and the availability of a wide range of biologic and targeted synthetic drugs. In this communication, we present new findings in the diagnosis and treatment of selected rheumatic diseases, specifically rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic scleroderma, idiopathic inflammatory myopathies, systemic vasculitis, rheumatic polymyalgia and giant cell arteritis, and osteoarthritis. This communication aims to provide a summary of the latest findings and trends in the diagnosis and treatment of these rheumatic diseases, which have a major impact on the quality of life of patients.

• MeSH
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis diagnosis   drug therapy   MeSH
• Antirheumatic Agents administration & dosage   pharmacology   therapeutic use   MeSH
• Axial Spondyloarthritis diagnosis   drug therapy   complications   MeSH
• Biological Therapy methods   MeSH
• Immunotherapy, Adoptive methods   MeSH
• Janus Kinase Inhibitors administration & dosage   pharmacology   therapeutic use   MeSH
• Immunoglobulins, Intravenous administration & dosage   therapeutic use   MeSH
• Methotrexate administration & dosage   therapeutic use   MeSH
• Antibodies, Monoclonal administration & dosage   pharmacology   therapeutic use   MeSH
• Myositis diagnosis   drug therapy   immunology   MeSH
• Giant Cell Arteritis diagnosis   drug therapy   MeSH
• Osteoarthritis diagnosis   drug therapy   MeSH
• Polymyalgia Rheumatica diagnosis   therapy   MeSH
• Arthritis, Psoriatic diagnosis   drug therapy   complications   MeSH
• Rheumatic Diseases * diagnosis   drug therapy   complications   MeSH
• Arthritis, Rheumatoid diagnosis   drug therapy   complications   MeSH
• Risk Factors MeSH
• Scleroderma, Systemic diagnosis   drug therapy   complications   MeSH
• Lupus Erythematosus, Systemic diagnosis   drug therapy   complications   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.

• MeSH
• Alleles MeSH
• Autoantibodies * genetics   MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Haplotypes MeSH
• HLA-DRB1 Chains genetics   MeSH
• Humans MeSH
• Myositis * genetics   immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article 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.

• MeSH
• Antirheumatic Agents pharmacology   MeSH
• Autoantibodies analysis   MeSH
• Humans MeSH
• Patient Care Management methods   MeSH
• Myositis * diagnosis   immunology   therapy   MeSH
• Severity of Illness Index MeSH
• Symptom Assessment methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.

• MeSH
• Alleles MeSH
• Autoantibodies genetics   immunology   MeSH
• White People genetics   MeSH
• Adult MeSH
• Genotype MeSH
• Haplotypes MeSH
• HLA-DRB1 Chains genetics   immunology   MeSH
• Major Histocompatibility Complex genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Myositis genetics   immunology   MeSH
• Polymorphism, Genetic MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS: Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. RESULTS: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2-7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. CONCLUSIONS: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

• MeSH
• Autoantibodies immunology   MeSH
• Dermatomyositis epidemiology   immunology   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Comorbidity MeSH
• Middle Aged MeSH
• Humans MeSH
• Myositis diagnosis   epidemiology   immunology   MeSH
• Disease Susceptibility immunology   MeSH
• Odds Ratio MeSH
• Polymyositis epidemiology   immunology   MeSH
• Prevalence MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

• MeSH
• Diagnostic Techniques and Procedures MeSH
• Adult MeSH
• Glucocorticoids therapeutic use   MeSH
• Clinical Laboratory Techniques methods   MeSH
• Drug Therapy, Combination MeSH
• Skin Manifestations MeSH
• Creatine Kinase analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Myositis * diagnosis   immunology   therapy   MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH