No abstract

Our results confirm the overexpression of IL-6 in dcSSc and support the potential of IL-6 as a surrogate marker for clinical outcome in this disease. The data also provide rationale for clinical studies targeting IL-6 trans-signalling as a potential antifibrotic therapy for SSc.

Objective To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. Methods Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. Results The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody–positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20‐year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti–Scl‐70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti‐Scl‐70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti‐Scl‐70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti–RNA polymerase antibody–positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti–U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. Conclusion These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.

SSc in overlap with ANCA-associated vasculitis is rare, and clinical features are more mixed than when either of these two conditions occurs separately. From our database, U3RNP antibodies may be more associated with overlap AAV than the other scleroderma-specific antibodies.

Intact TGFβ signaling in resident pulmonary fibroblasts is essential for pulmonary fibrosis to develop. Our data support a key regulatory role of these cells in determining fibrocyte recruitment and myofibroblast differentiation.

Objective: To compare the views of doctors and patients on whether doctors should wear white coats and to determine what shapes their views. Methods: A questionnaire study of 400 patients and 86 doctors was performed. Results: All 86 of the doctors' questionnaires were included in the analysis but only 276 of the patients were able to complete a questionnaire. Significantly more patients (56%) compared with their doctors (24%) felt that doctors should wear white coats (p,0.001). Only age (.70 years) (p,0.001) and those patients whose doctors actually wore white coats (p,0.001) were predictive of whether patients favoured white coats. The most common reason given by patients was for easy identification (54%). Less than 1% of patients believed that white coats spread infection.Only 13% of doctors wore white coats as they were felt to be an infection risk (70%) or uncomfortable (60%). There was no significant difference between doctor subgroups when age, sex, grade, and specialty were analysed. Conclusion: In contrast to doctors, who view white coats as an infection risk, most patients, and especially those older than 70 years, feel that doctors should wear them for easy identification. Further studies are needed to assess whether this affects patients' perceived quality of care and whether patient education will alter this view.

This study highlights the importance of reduced bioavailability of Axin-2 in mediating the increased canonical Wnt response observed in SSc fibroblasts. This novel mechanism extends our understanding of the processes involved in Wnt/β-catenin-driven pathology and supports the rationale for targeting the TGFβ pathway to regulate the aberrant Wnt signaling observed during fibrosis.

ObjectivesClinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease. We aimed to improve understanding of the molecular differences between key diffuse cutaneous SSc subgroups as defined by their SSc-specific autoantibodiesMethodsWe have used high-dimensional transcriptional and proteomic analysis of blood and the skin in a well-characterised cohort of SSc (n=52) and healthy controls (n=16) to understand the molecular basis of clinical diversity in SSc and explore differences between the hallmark antinuclear autoantibody (ANA) reactivities.ResultsOur data define a molecular spectrum of SSc based on skin gene expression and serum protein analysis, reflecting recognised clinical subgroups. Moreover, we show that antitopoisomerase-1 antibodies and anti-RNA polymerase III antibodies specificities associate with remarkably different longitudinal change in serum protein markers of fibrosis and divergent gene expression profiles. Overlapping and distinct disease processes are defined using individual patient pathway analysis.ConclusionsOur findings provide insight into clinical diversity and imply pathogenetic differences between ANA-based subgroups. This supports stratification of SSc cases by ANA antibody subtype in clinical trials and may explain different outcomes across ANA subgroups in trials targeting specific pathogenic mechanisms.