BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.
- MeSH
- antinukleární protilátky * krev MeSH
- DNA-topoisomerasy I imunologie MeSH
- dospělí MeSH
- klinická relevance MeSH
- lidé středního věku MeSH
- lidé MeSH
- průřezové studie MeSH
- senioři MeSH
- systémová sklerodermie * 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
- systematický přehled MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects. METHODS: In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqManTM Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip). RESULTS: Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA. CONCLUSION: The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA.
- MeSH
- biologické markery MeSH
- bolest MeSH
- cirkulující mikroRNA * MeSH
- lidé MeSH
- mikro RNA * MeSH
- osteoartróza * diagnostické zobrazování genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference 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.
