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
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
PREDUKA (PREventivně EDUKAční program proti relapsu psychózy) je šestihodinový profesionálně vedený skupinový program pro pacienty s psychotickým onemocněním v ambulantní léčbě a pro jejich blízké. V pilotní terénní dotazníkové studii jsme zmapovali využití praktických rad získaných na PREDUCE a teoretické znalosti absolventů programu. Zařadili jsme účastníky programu z let 2007-2009, soubor tvořilo 14 pacientů a 22 příbuzných. Průměrný věk pacientů byl 28,6 let, příbuzných 44,4 let. Znalosti absolventů o psychózách a jejich léčbě jsou velmi dobré, compUance pacientů z našeho souboru vysoká. Radami získanými na PREDUCE se účastníci obvykle řídí. Častá je neznalost důležitých telefonních čísel (krizové centrum, ošetřující psychiatr). Dlouhodobější skupinovou psychoedukaci by bylo vhodné nabídnout celým rodinám, protože příbuzní vyjadřují s komunikací v rodině ještě větší nespokojenost než sami pacienti.
PREDUKA (PREventive EDUcational programme for relapse prevention) is a six-hour professionally-led group programme for patients with psychotic disorders in outpatient care and for their relatives. In a field questionnaire survey we mapped usage of practic al advice obtained from PREDUKA and theoretical knowledge of participants. Participants from years 2007–2009 were included. The sample consisted of 14 patients and 22 relatives. The average age of patients was 28,6 years, that of relatives 44,4 years. Knowledge of participants about psychosis and their therapy is very good, compliance of patients from our sample is high. Participants usually follow adv ice obta- ined from PREDUKA. Common is the ignorance of important phone numbers (crisis centre, attending psychiatrist). A long term grou p psychoeducation would be suitable programme for whole families as relatives express even higher dissatisfaction with communicat ion within a family then patients themselves.
- Klíčová slova
- prevence relapsu, rodinná psychoedukace,
- MeSH
- adherence pacienta MeSH
- financování organizované MeSH
- kooperační chování MeSH
- lidé MeSH
- pacientův souhlas se zdravotní péčí psychologie MeSH
- průzkumy a dotazníky využití MeSH
- recidiva MeSH
- rodinná terapie metody MeSH
- rodinné vztahy MeSH
- schizofrenie diagnóza farmakoterapie MeSH
- sekundární prevence MeSH
- Check Tag
- lidé MeSH
Anti-PM-Scl protilátky se nejčastěji vyskytují u pacientů s překryvným syndromem polymyositidy a systémové sklerózy (31%), vzácněji při samotné myositidě (8–11%), nebo systémové skleróze (2%). Jejich průkaz bývá spojen s lepší prognózou onemocnění, které obvykle dobře reaguje na léčbu nízkými až středními dávkami glukokortikoidů. PM-Scl autoantigenem je “lidský exozóm”, makromolekulární komplex 11–16 polypeptidů, který se v buněčném jadérku účastní štěpení prekurzorové rRNA a v cytoplazmě pomáhá degradovat zralou mRNA. Primární protilátková reakce proti PM-Scl komplexu je namířena proti PMScl- 100 proteinu, jehož hlavním epitopem je PM1-? peptid.
Anti-PM-Scl antibodies are most frequently found in patients with overlap syndrome of polymyositis and systemic sclerosis (31%), less frequently in myositis alone (8–11%), or systemic sclerosis (2%). Detection of these antibodies is associated with better outcome of the disease, which usually responds well to the treatment with low- to medium-dose glucocorticoids. The “human exosome” is a PM-Scl autoantigen, a macromolecular complex of 11–16 polypeptides, which is involved in the degradation of precursor rRNA in the nucleolus and in the degradation of mature mRNA in the cytoplasm. Antibody response against the PM-Scl complex is primarily targeted against the PM-Scl-100 protein, the main epitope of which is PM1-? peptide.
- MeSH
- autoantigeny MeSH
- autoprotilátky genetika klasifikace MeSH
- financování organizované MeSH
- lidé MeSH
- myozitida imunologie patofyziologie MeSH
- polymyozitida MeSH
- systémová sklerodermie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
