OBJECTIVES: To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process. METHODS: 94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed. The mRNA expression level was determined using quantitative real-time PCR method. The expression of intracellular HSP70 was established by flow cytometry, the extracellular HSP70 protein was measured in plasma samples using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of HSPA1A gene was significantly up-regulated in patients with autoimmune diseases (SLE: p<0.01; SSc: p<0.01; IIM: p<0.0001) compared to healthy controls. The expression of HSPA1B gene was increased only in patients with myositis (p<0.05). Furthermore, the HSPA1B gene expression is associated with the HLA-DRB1*03 risk allele in patients with IIM. In addition, we have found a relation between HSPA1A gene expression regulation and the presence of disease specific autoantibodies in patients with SLE and myositis. The level of intracellular HSP70 was not increased; however, the level of extracellular HSP70 protein was increased in patients suffering from SSc and IIM as compared to controls. CONCLUSIONS: The results suggest an involvement of the MHC-linked HSP70 genes in the pathology of studied autoimmune disorders. Therefore, the HSPA1A and HSPA1B genes might serve as an interesting candidate molecule for development of distinct types of autoimmunities.

• MeSH
• alely MeSH
• autoimunita genetika   MeSH
• autoprotilátky MeSH
• biologické markery MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida genetika   imunologie   MeSH
• proteiny tepelného šoku HSP70 genetika   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• systémová sklerodermie genetika   imunologie   MeSH
• systémový lupus erythematodes genetika   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

OBJECTIVE: The PIWIL (P-element induced wimpy testis like protein) subfamily of argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and their function to silence transposons during germ-line development. Here we explored their presence and regulation in rheumatoid arthritis (RA). METHODS: The expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and Western blot. The expression of piRNAs was quantified by next generation small RNA sequencing (NGS). The regulation of PIWI/piRNAs, proliferation and methylation of LINE-1 after silencing of PIWIL genes were studied. RESULTS: PIWIL2 and 4 mRNA were similarly expressed in synovial tissues and SF from RA and OA patients. However, on the protein level only PIWIL4 was strongly expressed in SF. Using NGS up to 300 piRNAs were identified in all SF without significant differences in expression levels between RA and OASF. Of interest, the analysis of the co-expression of the detected piRNAs revealed a less tightly regulated pattern of piRNA-823, -4153 and -16659 expression in RASF. In RASF and OASF, stimulation with TNFα+IL1β/TLR-ligands further significantly increased the expression levels of PIWIL2 and 4 mRNA and piRNA-16659 was significantly (4-fold) induced upon Poly(I:C) stimulation. Silencing of PIWIL2/4 neither affect LINE-1 methylation/expression nor proliferation of RASF. CONCLUSION: We detected a new class of small regulatory RNAs (piRNAs) and their specific binding partners (PIWIL2/4) in synovial fibroblasts. The differential regulation of co-expression of piRNAs in RASF and the induction of piRNA/Piwi-proteins by innate immune stimulators suggest a role in inflammatory processes.

• MeSH
• Argonaut proteiny genetika   metabolismus   MeSH
• cytokiny metabolismus   MeSH
• dlouhé rozptýlené jaderné elementy MeSH
• fibroblasty patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• osteoartróza genetika   metabolismus   patologie   MeSH
• proteiny genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• revmatoidní artritida genetika   metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• synoviální membrána patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference 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

Abstract The aim of this study was to evaluate the role of S100A4 as a biomarker in patients with early rheumatoid arthritis (RA). S100A4 levels were measured in 59 patients with early RA and in 41 healthy controls. The association between the S100A4 levels and the treatment outcome after 12 months was determined using multivariate regression analysis. Serum S100A4 levels were significantly higher in the patients with early RA than in the healthy subjects and significantly decreased after 3 months of treatment. Diseases activity at 12 months was significantly higher in female patients who had initially high levels of S100A4. Persistently high S100A4 levels predicted poor treatment outcome and S100A4 may thus represent promising biomarker for assessing treatment response in patients with RA.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• proteiny S100 krev   MeSH
• revmatoidní artritida krev   farmakoterapie   patologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• výsledek terapie 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

a) Kvantitativní analýza sérových hladin BAFF (B cell activating factor of the TNF family) a exprese jeho receptorů (BAFF-R,TACI a BCMA) na imunologicky relevantních buňkách periferní krve a svalových infiltrátů v patogenetickém mechanizmu idiopatickýchzánětlivých myopatií ve vztahu k aktivitě onemocnění. b) Zhodnocení vztahu SNPs v promotorové oblasti BAFF genu k diagnóze a k hladině BAFF proteinu, s posouzením míry korelace mezi rizikovou alelou (genotypem) HLA-DRB1*03 a těchto polymorfismů (HLA matched case-control study). c) Posouzení vlivu standardní terapie na hladiny BAFF a exprese jeho receptorů a stanovení prediktivní hodnoty všech zkoumaných parametrů pro riziko vývoje symptomatické hypogamaglobulinemie při terapii glukokortikoidy. d) Zhodnocení možného využití těchto vyšetření k vytipování případných kandidátů na B-depleční, nebo BAFF blokující terapii mezi nemocnými s nedostatečnou odpovědí na standardní léčbu.; a) Quantitative analysis of serum levels of BAFF (B cell activating factor of the TNF family) and expression of its receptors (BAFF-R, TACI and BCMA) on immunologically relevant cells in peripheral blood and muscle infiltrate to pathogenetic mechanisms of idiopathic inflammatory myopathies in relation to disease activity. b) The evaluation of relation of BAFF gene promotor region SNPs to diagnosis and level of BAFF protein with assessment of the extent of correlation with risk HLA-DRB1*03 allele (genotype) and these polymorphisms (HLA matched case-control study). c) The assessment of influence of standard treatment on serum BAFF levels and on expression of its receptors and evaluation of predictive values of measured variables for risk of development of symptomatic hypogammaglobulinaemia during the treatment. d) The evaluation of possible application of these assays for selection of candidates for B-cell depleting or BAFF blocking treatment from patients with inadequate response to standard treatment.

• MeSH
• alternativní sestřih MeSH
• dermatomyozitida diagnóza   farmakoterapie   MeSH
• faktor aktivující B-buňky MeSH
• fluorescenční protilátková technika MeSH
• histidin-tRNA-ligasa antagonisté a inhibitory   MeSH
• intersticiální plicní nemoci diagnóza   farmakoterapie   MeSH
• maturační antigen B-buněk MeSH
• myozitida diagnóza   farmakoterapie   MeSH
• polymorfismus genetický MeSH
• polymyozitida diagnóza   farmakoterapie   MeSH
• receptor faktoru aktivujícího B-buňky diagnostické užití   MeSH
• receptor TACI MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• revmatologie
• vnitřní lékařství
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

OBJECTIVES: The aim of this study was a large scale investigation of myositis-associated circulating miRNA molecules and also determination of expression of these candidate molecules in relation to clinical activity of myositis. METHODS: RNA, containing also miRNAs, was isolated from sera of 28 patients suffering from idiopathic inflammatory myopathies (IIM) and 16 healthy controls. Expression of miRNAs was determined using a miRNA microarray method. Statistical analysis of miRNA expression was carried out using Arraystar software. RESULTS: Our results showed 23 significantly differentially expressed miRNAs. Six miRNAs were differentially expressed in IIM compared to healthy controls. In dermatomyositis (DM) we found 3 and in polymyositis (PM) 6 differentially expressed miRNAs compared to controls. Three miRNAs were up-regulated in patients with highly active disease compared to patients with low disease activity. Furthermore, we found 26 significantly differentially expressed miRNAs in SLE patients compared to IIM, DM and PM patients. CONCLUSIONS: This is the first study that comprehensively describes expression levels of circulating miRNAs in serum of patients suffering from IIM. It can be expected that some of these deregulated miRNA molecules are involved in aetiology of IIM and may potentially serve as molecular markers for IIM development or for monitoring of disease activity.

• MeSH
• dermatomyozitida krev   genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické markery MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   genetika   MeSH
• prediktivní hodnota testů MeSH
• regulace genové exprese MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů * MeSH
• software MeSH
• stanovení celkové genové exprese metody   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) is characterized by the predominant presence of necrotic muscle fibres in muscle biopsy and variable response to immunosuppressive treatment. The aims of this study were to analyse the temporal trend of IMNM incidence in our centre over the past 10 years and to explore the role of statins as possible causative agents. METHODS: A retrospective evaluation of muscle biopsy results, clinical and laboratory data, including antibody associations of all patients with idiopathic inflammatory myopathy newly diagnosed between 2004 and June 2014, was performed. Available sera were tested for the presence of anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) autoantibodies. RESULTS: Of 357 biopsied patients, 233 fulfilled criteria for inflammatory/immune-mediated myopathy, including 27 (11.6%) classified as IMNM. There were no patients with IMNM diagnosed between 2004 and 2007; subsequently, two to three cases of IMNM per year were seen during the period 2008-11, with a substantial increase to 18 cases (66.6% of all IMNM biopsies) in 2012-14. Thirteen of 27 patients (48%) had a history of statin use, 11 (85%) of whom had positive anti-HMGCR antibodies. There was no IMNM patient without a history of statin use who was anti-HMGCR antibody positive. CONCLUSION: Our data show an increasing incidence of IMNM, which is mainly accounted for by anti-HMGCR-positive IMNM associated with the use of statins.

• MeSH
• autoprotilátky krev   MeSH
• biopsie MeSH
• dospělí MeSH
• hydroxymethylglutaryl-CoA-reduktasy imunologie   MeSH
• incidence MeSH
• kosterní svalová vlákna patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida epidemiologie   MeSH
• nekróza MeSH
• nemoci svalů epidemiologie   imunologie   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• statiny škodlivé účinky   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
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis. METHODS: Serum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated. RESULTS: All myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (beta = 0.552; P = 0.002) in PM patients and with MYOACT (beta = 0.557; P = 0.003) and CRP levels (beta = 0.391; P = 0.029) in DM patients. CONCLUSIONS: Circulating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.

• MeSH
• autoprotilátky imunologie   krev   MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• dermatomyozitida diagnóza   krev   MeSH
• dospělí MeSH
• ELISA MeSH
• kreatinkinasa krev   MeSH
• L-laktátdehydrogenasa krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida * MeSH
• nádory * komplikace   krev   MeSH
• polymyozitida diagnóza   krev   MeSH
• proteiny S100 * MeSH
• S100 kalcium vázající protein A4 MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

OBJECTIVE: To evaluate circulating visfatin and its relationship with disease activity and serum lipids in patients with early, treatment-naïve rheumatoid arthritis (RA). METHODS: Serum visfatin was measured in 40 patients with early RA before and after three months of treatment and in 30 age- and sex-matched healthy individuals. Disease activity was assessed using the Disease Activity Score for 28 joints (DAS28) at baseline and at three and 12 months. Multivariate linear regression analysis was performed to evaluate whether improved disease activity is related to serum visfatin or a change in visfatin level. RESULTS: Serum visfatin was significantly elevated in early RA patients compared to healthy controls (1.92±1.17 vs. 1.36±0.93 ng/ml; p = 0.034) and significantly decreased after three months of treatment (to 0.99±0.67 ng/ml; p<0.001). Circulating visfatin and a change in visfatin level correlated with disease activity and improved disease activity over time, respectively. A decrease in visfatin after three months predicted a DAS28 improvement after 12 months. In addition, decreased serum visfatin was not associated with an improved atherogenic index but was associated with an increase in total cholesterol level. CONCLUSION: A short-term decrease in circulating visfatin may represent an independent predictor of long-term disease activity improvement in patients with early RA.

• MeSH
• antirevmatika terapeutické užití   MeSH
• C-reaktivní protein metabolismus   MeSH
• časové faktory MeSH
• cholesterol krev   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• lipidy krev   MeSH
• multivariační analýza MeSH
• nikotinamidfosforibosyltransferasa krev   MeSH
• revmatoidní artritida krev   farmakoterapie   patologie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie 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