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Cojocaru V.M.,Clinical Eye Emergency Hospital | Ciurtin C.,Ion Cantacuzino Clinical Hospital | Uyy E.,Institute of Cellular Biology and Pathology Nicolae Simionescu | Antohe F.A.,Institute of Cellular Biology and Pathology Nicolae Simionescu
Digest Journal of Nanomaterials and Biostructures | Year: 2011

Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by dry eye and mouth as a result of exocrine glands destruction due to lymphocytes and plasma cells infiltration. The aim of this study was to compare the protein profile in the tears of healthy subjects and patients with SS associated with rheumatoid arthritis (RA) in an effort to reveal potential biomarker candidates. The study groups consisted of subjects with SS associated with RA, patients with RA without SS and healthy volunteers. Tear fluids were collected by Schirmer method. The tear proteins were separated by electrophoresis and analysed by Nano-LC-nano-ESI-MS/MS. The results demonstrated that the patients with SS have significantly reduced values of Schirmer tests. The Coomassie colloidal blue staining evidenced only the most abundant peptides present in the tears from all groups analyzed with significant quantitative differences in the abundance of some peptides. The trypsin digestion and Nano-LC-nano-ESI-MS/MS sequencing were performed for a total of 27 different proteins identified in all tear samples. The proteomic technology proved to be a good strategy to characterize tear proteins patterns in normal subjects and in patients with different ocular dysfunction for the identification of potential biomarkers associated with chronic systemic diseases.

Hachulla E.,University of Lille Nord de France | Clerson P.,Orgametrie Biostatistiques | Airo P.,UO Reumatologia e Immunologia Clinica | Allanore Y.,University of Paris Descartes | And 18 more authors.
Rheumatology (United Kingdom) | Year: 2015

Objective. The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort.Methods. Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables.Results. Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and 36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI 1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg.Conclusion. An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Jordan S.,University of Zurich | Distler J.H.W.,Friedrich - Alexander - University, Erlangen - Nuremberg | Maurer B.,University of Zurich | Huscher D.,Charite University Hospital and German Rheumatism Research Center | And 37 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods: Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results: 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions: The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.

Maurer B.,University of Zurich | Graf N.,Graf Biostatistics | Michel B.A.,University of Zurich | Muller-Ladner U.,Justus Liebig University | And 162 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives To identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc). Methods An observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with p<0.2 were included in the logistic regression analysis. The prediction models were then validated in a second cohort. Results A total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate. Conclusions Our study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.

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