Dataset Information

The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis with/without Lofgren's Syndrome.

ABSTRACT: Purpose. Pulmonary sarcoidosis is associated with dysregulated expression of intracellular miRNAs. There is however only little information on extracellular miRNAs and their association with the disease course in sarcoidosis. We therefore assessed serum miRNAs in sarcoidosis classified according to the presence of Löfgren's syndrome (LS) as a hallmark of good prognosis in contrast to more advanced disease course. Methods. RT-PCR was used to assess 35 miRNAs in 13 healthy controls and 24 sarcoidosis patients (12 with X-ray (CXR) stage ? 1 and LS and 12 with insidious onset and CXR stage ? 3). Results. Compared to controls, we consistently observed dysregulated expressions of miR-146, miR-16, miR-425-5p, and miR-93-5p in both sarcoidosis groups irrespective of disease course. Specifically, patients without LS had dysregulated expressions of miR-150-5p, miR-1, and miR-212 compared to controls. Patients with LS had dysregulated expressions of miR-21-5p and miR-340-5p compared to controls. Bioinformatics predicted consistently "Pathways in cancer" to be modulated by both altered profiles in patients with/without LS. Three miRNAs (miR-21-5p, miR-340-5p, and miR-212-3p) differed between our patients with LS and those without LS; their cumulative effect may modulate "TGF-? signalling pathway." Conclusions. Further study should focus on possible applications of serum miRNAs for diagnostics follow-up and for prognosis.

SUBMITTER: Novosadova E

PROVIDER: S-EPMC5165170 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis with/without Löfgren's Syndrome.

Novosadova Eva E Chabronova Alzbeta A Kolek Vitezslav V Petrek Martin M Navratilova Zdenka Z

Mediators of inflammation 20161205

<i>Purpose</i>. Pulmonary sarcoidosis is associated with dysregulated expression of intracellular miRNAs. There is however only little information on extracellular miRNAs and their association with the disease course in sarcoidosis. We therefore assessed serum miRNAs in sarcoidosis classified according to the presence of Löfgren's syndrome (LS) as a hallmark of good prognosis in contrast to more advanced disease course. <i>Methods</i>. RT-PCR was used to assess 35 miRNAs in 13 healthy controls a ...[more]

PMID: 28050119

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Project description:BackgroundSarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects.MethodsCXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-γ-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function.ResultsIn a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p < 0.001). CXCL11 was positively correlated with CXCL9 and CXCL10 (p < 0.001), sedimentation rate (p < 0.01), and mean expression of three IFN-γ-related genes in whole blood (GBP1, STAT1, and STAT2) (p < 0.001). CXCL11 was inversely correlated with FVC %predicted (%pred) and FEV1 %pred and higher levels were associated with higher patient-reported dyspnea scores. We found positive correlations between CXCL11 and number of organs involved. Using survival analyses, we found that CXCL11 levels were predictive of future pulmonary function test (PFT) decline (log rank <0.001 and HR of log10(CXCL11) = 5.1, 95% CI 1.2-21, p = 0.026).ConclusionsThe pattern of expression of serum CXCL11 in sarcoidosis patients suggests that this blood measure could be helpful in identifying patients that need longer-term monitoring for progressive thoracic and extra-thoracic sarcoidosis.

Project description:BACKGROUND:Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs). METHODS:RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls. RESULTS:Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p?0.02) and HuR (p?0.03) proteins than control healthy PBTLs. CONCLUSION:mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis patients compared to healthy individuals. Its significance, e.g. for stability of mRNAs encoding pro-inflammatory factors, should be further explored in sarcoidosis.

Project description:PurposeReduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status.MethodsPhysical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King's Sarcoidosis Questionnaire (KSQ).ResultsPatients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p?<?0.01) and a trend towards fewer sit-to-stand transitions each day (p?=?0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p?<?0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r?=?0.634, p?=?0.01), but not with forced vital capacity (r?=?0.290), fatigue (r?=?0.041), dyspnoea (r?=?-0.466) or KSQ health status (r?=?0.099-0.484). Time spent upright was associated with fatigue (r?=?-0.630, p?=?0.012) and health status (KSQ Lung scores r?=?0.524, p?=?0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r?=?-0.527, p?=?0.044).ConclusionPhysical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

Dataset Information

The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis with/without Lofgren's Syndrome.

Publications

The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis with/without Löfgren's Syndrome.

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