High Baseline Serum Clara Cell 16 kDa Predicts Subsequent Lung Disease Worsening in Systemic Sclerosis.

Objective: Clara cell secretory protein (CC16) is a sensitive marker of bronchial epithelial cell damage. The CC16 serum level is elevated in patients with pulmonary fibrosis, but its predictive value on lung disease progression has not yet been studied. We aimed to assess the value of serum CC16 concentration in predicting lung disease deterioration in patients with systemic sclerosis (SSc).

Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis.

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide () is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning into membrane conductance (diffusing capacity) for carbon monoxide () and alveolar capillary blood volume () through combined measurement of and transfer factor of the lung for nitric oxide () is more effective to identify pulmonary hypertension in SSc patients compared with alone. Here, the objective was to determine whether combined - partitioned with recently refined equations could more accurately detect pulmonary hypertension than alone in SSc.

The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients.

Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus.

In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.

RhoA/Rho-kinase activation promotes lung fibrosis in an animal model of systemic sclerosis.

Background: Systemic sclerosis (SSc) is a connective-tissue disease characterized by vascular injury, immune-system disorders, and excessive fibrosis of the skin and multiple internal organs. Recent reports found that RhoA/Rho-kinase (ROCK) pathway is implicated in various fibrogenic diseases. Intradermal injection of hypochlorous acid (HOCl)-generating solution induced inflammation, autoimmune activation, and fibrosis, mimicking the cutaneous diffuse form of SSc in humans.

Increased exhaled nitric oxide precedes lung fibrosis in two murine models of systemic sclerosis.

Exhaled nitric oxide (NO) is increased as a result of lung inflammation, which in turn causes subsequent interstitial lung disease in patients with systemic sclerosis (SSc). However, the exact time course of inflammatory and fibrotic changes in the SSc lung has not yet been described. Our objective was to assess the chronological evolution of lung inflammatory and fibrotic processes in mice pre-treated with hypochlorous acid (HOCl) or bleomycin.

[Periungueal capillaroscopy: an easy and reliable method to evaluate all microcirculation diseases].

Periungueal capillaroscopy is a simple and reliable non-invasive technique allowing evaluation of cutaneous microcirculation. It was promoted for decades in patients with Raynaud's phenomenon in order to differentiate between the benign primary Raynaud's phenomenon and the secondary form in connective tissue diseases, especially systemic sclerosis. Nevertheless, the value of this procedure has also been shown in numerous pathologies such as diabetes or cardiovascular diseases.

[Use of pulmonary function tests and biomarkers studies to diagnose and follow-up interstitial lung disease in systemic sclerosis].

Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc.

Exhaled NO predicts cyclophosphamide response in scleroderma-related lung disease.

Cyclophosphamide (CYC) is not always effective in patients with scleroderma-related interstitial lung disease (SSc-ILD), hence the need for biomarkers able to predict beneficial responses to CYC therapy. We therefore assessed whether baseline alveolar concentration of nitric oxide (CANO) could predict the favourable response to CYC therapy in patients with SSc-ILD. Nineteen non-smoker patients with SSc-ILD, were enrolled and treated with 6 courses of CYC (0.

Successful use of infliximab therapy in sight-threatening corticosteroid-resistant Vogt-Koyanagi-Harada disease.

Purpose: To report an experience with infliximab in severe corticosteroid-resistant Vogt-Koyanagi-Harada (VKH) disease.

Design: Interventional case series.

Methods: The medical records of 2 adult patients were reviewed.

Association study of CRP gene in systemic sclerosis in European Caucasian population.

Opsonization and apoptotic cell elements are critical in systemic lupus erythematosus (SLE) and could act through the activation of the innate immunity. C-reactive protein (CRP) belongs to opsonins, and polymorphisms of CRP gene have been shown to be associated with SLE susceptibility. Accumulating evidences show that SLE and systemic sclerosis (SSc) share some genetic susceptibility factors.

Detection of alveolar fibrocytes in idiopathic pulmonary fibrosis and systemic sclerosis.

Background: Fibrocytes are circulating precursors for fibroblasts. Blood fibrocytes are increased in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to determine whether alveolar fibrocytes are detected in broncho-alveolar lavage (BAL), to identify their prognostic value, and their potential association with culture of fibroblasts from BAL.

[High plasmatic concentration of vitamin B12: an indicator of hepatic diseases or tumors].

Purpose: To identify the diseases that are associated with a high plasma concentration of vitamin B12 and to measure the strength of this association.

Patients And Methods: Retrospective study including all admissions between 1st May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal medicine, acute geriatrics and medical intensive care) with a test for plasma vitamin B12. The association between each of medical information system codes (solid tumors, malignant hematologic process, and renal disease) and a high or low vitamin B12 concentration was measured by odds ratios (OR) from logistic models taking into account repeated admissions, with adjustment for age and the weighted Charlson index.

High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma.

Alveolar concentration of nitric oxide (C(A)NO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of C(A)NO and the presence of inflammatory cells in alveoli. We have therefore measured C(A)NO and performed broncho-alveolar lavage (BAL) in SSc patients.

TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients.

Introduction: Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH.

Objective: To explore the genetic bases of SSc-PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members.

[Pulmonary embolism revealed by a seizure: a case report and literature review].

Introduction: Pulmonary embolism is a frequent disorder with a diagnostic approach based on probability estimation. Nevertheless, in some cases, prognosis may be impaired by delayed diagnosis resulting from atypical presenting manifestations.

Case Report: We report a 37-year-old woman, admitted for a seizure as the presenting manifestation of pulmonary embolism, and review nine additional similar cases reported in the literature since 1945.

Aldolase predicts subsequent myopathy occurrence in systemic sclerosis.

Introduction: Myopathy related to systemic sclerosis (Myo-SSc) is a disabling and unpredictable complication of SSc. We assessed the predictive value of serum aldolase, creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and C-reactive protein (CRP) to estimate the risk of developing Myo-SSc.

Methods: We enrolled 137 SSc patients without proximal muscle weakness in a prospective monocentric study to follow them longitudinally over a four-year period.

Comparing HLA shared epitopes in French Caucasian patients with scleroderma.

Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77), shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient's clinical subtypes and autoantibody status.

[Inflammatory aortitis in giant cell arteritis].

A sub-clinical inflammatory aortitis is very frequent in patients with giant cell arteritis, and can be the only localization of the disease. In most patients, this aortitis is asymptomatic and is of no consequence on the patient's survival. The relative risk of developing an aortic dissection or aneurysm is 17.

Brief report: candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity.

Objective: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) share some pathophysiologic bases as evidenced by individual and familial polyautoimmunity and common susceptibility genetic factors. With regard to the latter, there has been a recent shift from the "common variant" to the "rare variant" paradigm, since rare variants of TNFAIP3 and TREX1 with large effect sizes have recently been discovered in SLE. The present study was undertaken to investigate whether rare variants of TNFAIP3 and TREX1 are also associated with SSc.

Independent replication and meta analysis of association studies establish TNFSF4 as a susceptibility gene preferentially associated with the subset of anticentromere-positive patients with systemic sclerosis.

Objective: Independent replication with large cohorts and metaanalysis of genetic associations are necessary to validate genetic susceptibility factors. The known tumor necrosis factor (ligand) superfamily, member 4 gene (TNFSF4) systemic lupus erythematosus (SLE) risk locus has been found to be associated with systemic sclerosis (SSc) in 2 studies, but with discrepancies between them for genotype-phenotype correlation. Our objective was to validate TNFSF4 association with SSc and determine the subset with the higher risk.

Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis.

Objective: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc.

Methods: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied.