• Klíčová slova
• golimumab, tocilizumab, anakira, canakinumab,
• MeSH
• abatacept terapeutické užití   MeSH
• adalimumab terapeutické užití   MeSH
• biologická terapie * MeSH
• biosimilární léčivé přípravky terapeutické užití   MeSH
• dermatomyozitida imunologie   terapie   MeSH
• etanercept terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• interleukin-6 terapeutické užití   MeSH
• juvenilní artritida imunologie   terapie   MeSH
• lidé MeSH
• pediatrie MeSH
• revmatologie MeSH
• rituximab aplikace a dávkování   terapeutické užití   MeSH
• systémový lupus erythematodes imunologie   terapie   MeSH
• Check Tag
• lidé MeSH

We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub-study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6-month abatacept treatment were included in this sub-study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real-life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment-specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index-2 (FI-2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.

• MeSH
• abatacept terapeutické užití   MeSH
• dermatomyozitida krev   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• podskupiny B-lymfocytů účinky léků   MeSH
• polymyozitida krev   farmakoterapie   imunologie   MeSH
• T-lymfocyty - podskupiny účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie 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
• autoprotilátky imunologie   MeSH
• dermatomyozitida epidemiologie   imunologie   MeSH
• dospělí MeSH
• kohortové studie MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida diagnóza   epidemiologie   imunologie   MeSH
• náchylnost k nemoci imunologie   MeSH
• odds ratio MeSH
• polymyozitida epidemiologie   imunologie   MeSH
• prevalence 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
• Geografické názvy
• Evropa MeSH

• MeSH
• ankylózující spondylitida diagnostické zobrazování   MeSH
• Behcetův syndrom farmakoterapie   MeSH
• dermatomyozitida farmakoterapie   imunologie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• osteoporóza farmakoterapie   chemicky indukované   MeSH
• psoriatická artritida farmakoterapie   MeSH
• revmatické nemoci * farmakoterapie   MeSH
• systémová sklerodermie imunologie   terapie   MeSH
• systémový lupus erythematodes farmakoterapie   MeSH
• thalidomid analogy a deriváty   farmakologie   terapeutické užití   MeSH
• vakcíny proti chřipce aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: B-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity. METHODS: Serum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 anti-Jo-1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3-5 time points (23 cases) were included. Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM). RESULTS: Cross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels. PA revealed direct effects of anti-Jo-1 antibodies on CK (β = 0.41) and both direct (β = 0.42) and indirect (through anti-Jo-1 antibodies; β = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Δ) were associated with Δmyoglobin and Δaminotransferases and changes of BAFF correlated with ΔCK, Δcutaneous, Δmuscle, Δglobal, and Δskeletal disease activities. The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%). The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities. CONCLUSION: Our findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.

• MeSH
• antinukleární protilátky krev   MeSH
• dermatomyozitida krev   imunologie   patologie   MeSH
• dospělí MeSH
• faktor aktivující B-buňky krev   MeSH
• histidin-tRNA-ligasa imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie 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

Článek přináší přehled základních autoimunitních chorob, které vznikají v důsledku selhání tolerance k vlastním tkáním. Pojednává o mechanizmech imunologické tolerance, principech a fázích vzniku autoimunitního onemocnění. Přináší přehled výskytu protilátek více či méně charakteristických pro jednotlivá autoimunitní onemocnění.

Article provides a summary of autoimmune diseases that result from the failure of tolerance to self tissues. It discusses the mechanisms if immunological tolerance, principles and stages of formation of autoimmune disease. It provides an overview of the incidence of autoantibodies more or less characteristic for individual autoimmune diseases.

• MeSH
• autoimunita MeSH
• autoimunitní hepatitida imunologie   MeSH
• autoimunitní nemoci * etiologie   imunologie   klasifikace   MeSH
• autoprotilátky MeSH
• autotolerance fyziologie   genetika   účinky léků   MeSH
• celiakie imunologie   MeSH
• dermatomyozitida imunologie   MeSH
• imunologické faktory MeSH
• lidé MeSH
• revmatoidní artritida imunologie   MeSH
• systémová sklerodermie imunologie   MeSH
• systémový lupus erythematodes imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• imunopatogeneze, netóza,
• MeSH
• apoptóza imunologie   MeSH
• biologická terapie MeSH
• dermatomyozitida imunologie   komplikace   patofyziologie   MeSH
• extracelulární matrix imunologie   patologie   MeSH
• lidé MeSH
• pojivová tkáň * imunologie   patofyziologie   MeSH
• polymyozitida imunologie   komplikace   patofyziologie   MeSH
• revmatoidní artritida diagnóza   farmakoterapie   genetika   imunologie   patofyziologie   terapie   MeSH
• ribonukleoproteiny analýza   imunologie   MeSH
• smíšené onemocnění pojiva imunologie   patofyziologie   MeSH
• systémová sklerodermie etiologie   imunologie   patofyziologie   patologie   MeSH
• systémový lupus erythematodes diagnóza   genetika   imunologie   patofyziologie   terapie   MeSH
• zánět * imunologie   klasifikace   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

• MeSH
• autoprotilátky imunologie   MeSH
• dermatomyozitida imunologie   MeSH
• interferon typ I metabolismus   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida s inkluzními tělísky imunologie   MeSH
• prospektivní studie MeSH
• proteiny vázající RNA imunologie   MeSH
• senioři MeSH
• signální transdukce MeSH
• specificita protilátek * MeSH
• systémový lupus erythematodes imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVES: The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. METHODS: Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. RESULTS: Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). CONCLUSIONS: In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.

• MeSH
• 5'-nukleotidasa imunologie   MeSH
• autoimunitní nemoci imunologie   MeSH
• autoprotilátky imunologie   MeSH
• dermatomyozitida diagnóza   imunologie   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida s inkluzními tělísky diagnóza   imunologie   MeSH
• neuromuskulární nemoci imunologie   MeSH
• polymyozitida diagnóza   imunologie   MeSH
• revmatoidní artritida imunologie   MeSH
• ROC křivka MeSH
• roztroušená skleróza imunologie   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Sjögrenův syndrom imunologie   MeSH
• studie případů a kontrol MeSH
• systémová sklerodermie imunologie   MeSH
• systémový lupus erythematodes imunologie   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
• srovnávací studie MeSH

Intravenózní imunoglobulin (IVIG) je často Indikován u různých neurologických onemocnění. Nejčastější využití je u autoimunítních nervosvalových chorob. Jeho mechanismus účinku je komplexní s ovlivněním humorální i buněčné imunity.Kontrolované klinlcké studie prokazují efekt IVIG u většiny autoimunítních nervosvalových chorob. U Guillainova-Barréova syndromu je IVIG a léčebná plazmaferéza léčbou první volby a mají stejnou účinnost (síla doporučení A). Léčbu IVIG provází méně vedlejších účinků, a proto se mu dává přednost (síla doporučení B). U chronické zánětlivé demyelinizační polyneuropaťie se středně těžkou až těžkou disabllitou je vhodné použít jako léčbu 1. volby IVIG nebo kortikoidy (síla doporučení A). Vzhledem k chyběni alternativní léčby je IVIG u multifokální motorické neuropatie lékem první volby (síla doporučení A). U myasthenia gravis je léčba exacerbace léčebnou plazmaferézou i IVIG stejně účinná (síla doporučení A). Podávání IVIG se doporučuje u dermatomyozitidyjako léčba třetí linie v kombinaci s prednísonem, a tou pacientů, u kterých se po adekvátní terapií kortikoidy a jejich kombinací s imunosupresivy neprojevil dostatečný efekt léčby (síla doporučení B). IVIG má příznivý léčebný profil. Jeho vysoká cena je kompenzována nižšími náklady na intenzivní a následnou péči a zvýšenou kvalitou života.

Intravenous immunoglobulin (IVIG) is often indicated for various neurological diseases. The most common use is for the treatment of autoimmune neuromuscular diseases. Its mechanism of action is complex with effects on humoral and cellular immunity. Controlled clinical trials have proven the effect of IVIG on the majority of autoimmune neuromuscular diseases. In Guillain-Barré syndrome, IVIG and plasmapheresis are the first choice treatments, having the same efficacy (strength A recommendation). However, IVIG therapy is accompanied by fewer side effects, and is therefore preferred (strength B recommendation). In chronic inflammatory demyelinating polyneuropathy with moderate to severe disabílíty, IVIG or corticosteroids (strength A recommendation) are both recommended as the first choice treatment. Due to the lack of alternative treatment in multifocal motor neuropathy, IVIG is the drug of first choice (strength A recommendation). In the treatment of myasthenia gravis exacerbation, plasmapheresis and IVIG have the same effect (strength A recommendation). In patients with dermatomyositis who did not show sufficient improvement after adequate glucocorticoid therapy combined with immunosuppressive agents (strength B recommendation), the administration of IVIG is recommended as a third-line treatment in combination with prednisone. IVIG has a favourable therapeutic profile. Its high price is compensated by lower costs of intensive and follow-up care, and by increased quality of life.

• Klíčová slova
• zánětlivé polyneuropatie, zánětlivé myopatie,
• MeSH
• autoimunitní nemoci nervového systému etiologie   farmakoterapie   imunologie   MeSH
• dermatomyozitida etiologie   farmakoterapie   imunologie   MeSH
• Guillainův-Barrého syndrom etiologie   farmakoterapie   imunologie   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• Lambertův-Eatonův myastenický syndrom etiologie   farmakoterapie   imunologie   MeSH
• lidé MeSH
• myasthenia gravis etiologie   farmakoterapie   imunologie   MeSH
• myozitida etiologie   farmakoterapie   imunologie   MeSH
• neuromuskulární nemoci etiologie   farmakoterapie   imunologie   MeSH
• pohybová aktivita účinky léků   MeSH
• polyneuropatie etiologie   farmakoterapie   imunologie   MeSH
• poruchy nervosvalového přenosu farmakoterapie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH