OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.

• MeSH
• abatacept terapeutické užití   MeSH
• antirevmatika * terapeutické užití   MeSH
• biologické přípravky * terapeutické užití   MeSH
• imunomodulace MeSH
• lidé MeSH
• revmatoidní artritida * farmakoterapie   MeSH
• Torque teno virus * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

PURPOSE OF REVIEW: Idiopathic inflammatory myopathies (IIMs), known also as myositis, represent challenging group of heterogeneous muscle disorders characterized by symmetric proximal muscle weakness and evidence of muscle inflammation. The purpose of this review is to provide important updates on cytokines and inflammatory mediators related to myositis. RECENT FINDINGS: In the past 5 years, multiple studies brought a fresh insight into the pathogenesis of myositis by introducing new factors or further characterizing the role of the well established mediators in myositis. Among the mediators reviewed in this article, special attention was paid to interferons, C-X-C motif chemokine ligand 10, interleukin-18 and the IL23/Th17 axis. Some of the recent work has also focused on the nontraditional cytokines, such as adipokines, myokines, S100 proteins, High Mobility Group Box 1 or B-cell activating factor and on several anti-inflammatory mediators. Moreover, microRNAs and their potential to reflect the disease activity or to regulate the inflammatory processes in myositis have recently been subject of intensive investigation. Some of the above-mentioned mediators have been proposed as promising clinical biomarkers or therapeutic targets for myositis. SUMMARY: Several recent studies contributed to a better understanding of the pathogenesis of myositis and highlighted the clinical significance of certain inflammatory mediators. Application of these new findings may help to develop innovative approaches for patients' phenotyping, disease activity monitoring and potentially novel therapies.

• MeSH
• biologické markery krev   MeSH
• cirkulující mikroRNA krev   MeSH
• cytokiny krev   MeSH
• dermatomyozitida krev   diagnóza   MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• myozitida krev   diagnóza   MeSH
• svalová slabost krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Objectives: Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. Methods: The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. Results: In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P < 0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P < 0.0001). Conclusion: Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.

• MeSH
• ABC transportér z rodiny G, člen 2 genetika   MeSH
• alely MeSH
• běloši genetika   MeSH
• dna (nemoc) genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetická variace MeSH
• hyperurikemie genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• logistické modely MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové proteiny genetika   MeSH
• původní obyvatelé Havajských a ostatních tichomořských ostrovů genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Nový Zéland MeSH
• Spojené království MeSH

• MeSH
• ABC transportéry genetika   metabolismus   MeSH
• dna (nemoc) * genetika   metabolismus   patofyziologie   MeSH
• lidé MeSH
• molekulární biologie MeSH
• nádorové proteiny genetika   metabolismus   MeSH
• pohybová aktivita fyziologie   MeSH
• polymorfismus genetický * MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim of this study was to evaluate serum levels of visfatin in anti-Jo-1-positive myositis patients, its expression in muscle tissue and to investigate potential relationships between visfatin, B-cell activating factor of the TNF family (BAFF), disease activity and anti-Jo-1 autoantibody levels. METHODS: Serum levels of visfatin and BAFF were measured in 38 anti-Jo-1 positive myositis patients and 35 healthy subjects. Disease activity was evaluated by myositis disease activity assessment tool (MYOACT) using visual analogue scales (VAS) and by serum muscle enzymes. Visfatin expression was evaluated by immunohistochemistry in muscle tissue of myositis patients (n=10) and compared with non-inflammatory control muscle tissue samples from patients with myasthenia gravis (n=5). RESULTS: Serum visfatin and BAFF levels were significantly higher in myositis patients compared to healthy subjects and were associated with clinical muscle activity assessed by VAS. Only serum BAFF levels, but not visfatin levels, positively correlated with muscle enzyme concentrations and anti-Jo1 antibody levels. There was a positive correlation between visfatin and BAFF serum levels in myositis patients but a negative correlation was observed in healthy subjects. Visfatin expression was up-regulated in endomysial and perimysial inflammatory infiltrates of muscle tissue from myositis patients. CONCLUSIONS: Up-regulation of visfatin in myositis muscle tissue and an association between increased visfatin levels and muscle disease activity evaluated by MYOACT in anti-Jo-1 positive myositis patients could support possible role of visfatin in the pathogenesis of myositis.

• MeSH
• antinukleární protilátky krev   MeSH
• cytokiny analýza   krev   fyziologie   MeSH
• dospělí MeSH
• faktor aktivující B-buňky analýza   MeSH
• kosterní svaly chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida etiologie   imunologie   metabolismus   MeSH
• nikotinamidfosforibosyltransferasa analýza   krev   fyziologie   MeSH
• senioři MeSH
• vizuální analogová stupnice 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

• Publikační typ
• abstrakt z konference MeSH