Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis.

Objectives: The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study.

Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients.

Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility.

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.

Methods: Sixty-six non-HLA SNPs showing a P value <10⁻⁴ in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs.

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis.

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes.

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor.

Introduction: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.

Influence of the IL6 gene in susceptibility to systemic sclerosis.

Objective: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.

Pulmonary hypertension in systemic lupus erythematosus: prevalence, predictors and diagnostic strategy.

Objectives: To investigate the prevalence and predictors of pulmonary hypertension (PH) in patients with systemic lupus erythematosus (SLE) and to validate a diagnostic strategy.

Methods: 245 patients with SLE entered a screening program. Possible PH was defined as two consecutive systolic pulmonary arterial pressure (PAP) values ≥ 40mmHg by echocardiography.

Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis.

Objective: Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features.

Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.

Objectives: The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.

Methods: A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.

Bosentan in clinical practice for treating digital and other ischemic ulcers in Spanish patients with systemic sclerosis: IBER-DU cohort study.

Objective: To describe treatment outcomes and safety experience with bosentan in patients with systemic sclerosis (SSc) and digital ulcers (DU), in a clinical setting in Spain.

Methods: This was a multicenter, noninterventional retrospective cohort study. Data were collected retrospectively from patients with DU, with or without pulmonary arterial hypertension (PAH), who were initiating bosentan therapy in 2003 (n = 26) or 2004 (n = 41) and followed until May 2005.

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort.

Objectives: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.

Methods: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.

Changes in vitamin D levels in patients with systemic lupus erythematosus: Effects on fatigue, disease activity, and damage.

Objective: To analyze whether changes in serum 25-hydroxyvitamin D (25[OH]D) levels affect activity, irreversible organ damage, and fatigue in systemic lupus erythematosus (SLE).

Methods: We performed an observational study of 80 patients with SLE included in a previous cross-sectional study of 25(OH)D, reassessed 2 years later. Oral vitamin D(3) was recommended in those with low baseline 25(OH)D levels.

Predictors of major infections in systemic lupus erythematosus.

Introduction: Infections commonly complicate the course of systemic lupus erythematosus (SLE). Our aim is to investigate the clinical predictors of major infections in patients with SLE.

Methods: A nested case-control study design was used within the prospective Lupus-Cruces cohort.

Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus.

Fluctuations in the titers of anticardiolipin antibodies (aCL) have been reported in systemic lupus erythematosus (SLE) patients, but their relation with thrombosis is not completely understood. Prospective inception cohort of 237 patients with SLE (American College of Rheumatology criteria). Positivity for antiphospholipid antibodies (aPL) was defined according to Sapporo criteria.

High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus.

Background: Thrombosis is a frequent cause of morbidity and death in patients with systemic lupus erythematosus (SLE). Whether antiphospholipid syndrome (APS) is the cause of increased irreversible organ damage and mortality in lupus patients is not well established.

Methods: Prospective inception cohort of 202 patients with SLE (American College of Rheumatology criteria).