Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

Importance: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials.

Objective: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide.

Design, Setting, And Participants: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility.

Increased respiratory drive relates to severity of dyspnea in systemic sclerosis.

Background: Dyspnea may be a presenting symptom in progressive systemic sclerosis (SSc). Respiratory drive (mouth occlusion pressure, MOP, at rest and during CO2 rebreathing, 7% CO2, 93% O2) is a major determinant of dyspnea and may relate to the magnitude of dyspnea.

Methods: In a prospective design, MOP at 0.

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region.

Health-care utilization in Dutch systemic sclerosis patients.

This study aims to examine healthcare utilization and its determinants among patients with systemic sclerosis (SSc). A cross-sectional survey among all patients with SSc visiting an outpatient clinic of an academic hospital in the Netherlands was done. Assessments included sociodemographic characteristics and a survey on healthcare utilization including a registration of contacts with healthcare services since onset of disease, contacts, and number of visits with healthcare services over the last 12 months.

Translation, cross-cultural adaptation, and validation of the Mouth Handicap in Systemic Sclerosis questionnaire (MHISS) into the Dutch language.

The Mouth Handicap in Systemic Sclerosis (MHISS) is a French-generic questionnaire evaluating mouth-opening restriction, dryness, and esthetic concerns. The aim of this study was to translate and adapt the MHISS questionnaire into the Dutch language and evaluate its psychometric properties. The MHISS was translated according to international guidelines, field-tested among 16 systemic sclerosis (SSc) patients, and adapted.

Communication between human mast cells and CD4(+) T cells through antigen-dependent interactions.

Mast cells (MCs) are immune cells residing in tissues where pathogens are first encountered. It has been indicated that MCs might also be involved in setting the outcome of T-cell responses. However, little is known about the capacity of human MCs to express MHC class II and/or to capture and present antigens to CD4(+) T cells.

New insight on the Xq28 association with systemic sclerosis.

Objective: To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2).

Methods: We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays.

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.

Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study.

Introduction: A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry.

Methods: 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study.

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis.

Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc).

Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.

Introduction: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population.

Methods: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls.

Diagnosis and mortality prediction in pulmonary hypertension: the value of the electrocardiogram-derived ventricular gradient.

Purpose: The aim of this study was to investigate the use of the electrocardiogram-derived ventricular gradient, projected on the x-axis (VGx), for detection of pulmonary hypertension (PH) and for prediction of all-cause mortality in PH patients.

Methods: In patients referred for PH screening (n = 216), the VGx was calculated semiautomatically from the electrocardiogram and was defined as abnormal when less than 24 mV · ms. The VGx of PH patients was compared with the VGx of patients without PH.

Left ventricular dysfunction assessed by speckle-tracking strain analysis in patients with systemic sclerosis: relationship to functional capacity and ventricular arrhythmias.

Objective: Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, including cardiac manifestations, can lead to severe clinical complications, such as congestive heart failure, arrhythmias, and sudden death. Conventional echocardiography parameters have limited sensitivity to detect subtle myocardial dysfunction in patients with SSc.

Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study.

Introduction: Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses.

The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis.

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc.