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Objectives Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relationship between clinical signs of PVOD and severity of pulmonary vasculopathy in SSc. Methods This study included 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities [mean pulmonary arterial pressure (mPAP) >20 mmHg, pulmonary vascular resistance >2 WU or pulmonary artery wedge pressure (PAWP) >15 mmHg]. A chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0–1 group and the 2–3 group, according to the number of chest CT signs for PVOD, including mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function and serum biomarkers were compared between the two groups. Results Mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity were observed in 11 (21%), 32 (62%) and 11 (21%) patients, respectively. The 2–3 group (n  = 15) had higher mPAP (P  = 0.02) but lower diffusing capacity of carbon monoxide (DLCO)/alveolar volume (P  = 0.02) compared with the 0–1 group (n  = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide and Krebs von den Lunge-6 were not different between the two groups. Conclusions The CT signs for PVOD had a positive correlation with mPAP but a negative correlation with DLCO in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein. [ABSTRACT FROM AUTHOR]

Objective To investigate outcomes following the tapering or discontinuation of tocilizumab in patients with diffuse cutaneous SSc (dcSSc) in a real-world setting. Methods Fifteen patients who were treated with tocilizumab for dcSSc were selected from a single-centre cohort database and were evaluated for serial changes in the modified Rodnan total skin thickness score (mRSS) and predicted forced vital capacity (FVC) and the occurrence of clinical worsening events after the introduction of tocilizumab. Results Over 12 months of treatment with tocilizumab, the mRSS decreased from 20.4 ± 10.7 to 12.3 ± 8.5 (P   =  0.003) and FVC increased from 84.3 ± 13.7% to 88.5 ± 16.4% (P   =  0.04). Tocilizumab was tapered or discontinued in seven and three patients, respectively, after improvement in skin thickening without occurrence or progression of organ manifestations. One (14%) of seven patients who underwent tocilizumab tapering experienced a worsening of skin thickening, while all three patients who discontinued tocilizumab experienced a worsening of skin thickening and/or new development of pericarditis, arthritis, interstitial lung disease or pulmonary arterial hypertension. The additional patient who discontinued tocilizumab due to an adverse event experienced subsequent progression of multiple organ manifestations, including skin, lung, lower gastrointestinal and renal involvement, leading to mortality. Conclusion Our findings suggest potential benefits of prolonged tocilizumab use in dcSSc patients. The discontinuation of tocilizumab can lead to the progression of skin and visceral manifestations. Tapering rather than the discontinuation of tocilizumab is a viable option in dcSSc patients who experience remarkable clinical improvement. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC)., Methods: This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within 2 days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or haemodialysis dependence at discharge., Results: Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs 49.0%; odds ratio, 0.69; 95% CI: 0.48, 1.00; P = 0.049)., Conclusions: The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or haemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective. Although several miRNAs have been shown to regulate autoimmune pathogenesis by affecting lymphocyte function, the roles of miRNAs in the pathogenesis of SSc remain unclear. Therefore the purpose of this study was to identify miRNAs that play a role in the pathogenesis of SSc by quantitative PCR screening of serum miRNAs.Methods. Ninety-five miRNAs that were predicted to target SSc-related genes [IL-4, TGF-β, CTGF, PDGF-B, PDGF receptor (PDGFR) α/β and COL1A2) by in silico analyses were selected. The expression of these miRNAs in sera of SSc patients and healthy controls was measured by quantitative PCR. Involvement of miR-30b, which was most strongly down-regulated in SSc patients, in the regulation of PDGFR-β expression was examined by transfection experiments and 3′-untranslated region (3′-UTR) target luciferase assays. The expression of miR-30b in skin was evaluated in a bleomycin-induced dermal fibrosis model in mice and in SSc patients.Results. Nineteen of 95 miRNAs were significantly decreased in the sera of SSc patients. Among them, miR-30b was most strongly down-regulated in SSc patients (P = 0.00006) and the levels of miR-30b were inversely correlated with modified Rodnan skin scores. Transfection of a miR-30b mimic repressed PDGFR-β expression in dermal fibroblasts and the activity of a luciferase reporter containing 3′-UTR of PDGFR-β. Moreover, the expression of miR-30b was down-regulated in bleomycin-treated sclerotic skin and in affected skin in SSc patients.Conclusion. Down-regulation of miR-30b might be involved in the pathogenesis of SSc. [ABSTRACT FROM PUBLISHER]

Objective. Interstitial lung disease (ILD) is a serious complication of SSc. We aimed to identify markers associated with SSc-related ILD.Methods. RNA was prepared from the peripheral blood mononuclear cells of 14 SSc patients, divided into four different RNA pools according to the presence or absence of ILD and to the treatment, and subjected to microarray analysis. Real-time quantitative PCR was used to confirm the microarray results in 43 SSc patients, 42 autoimmune controls and 10 healthy controls. Genomic DNA samples were collected from 149 patients with SSc (70 in Hokkaido and 79 in Tokyo) who underwent a high-resolution CT for the evaluation of ILD and from 230 healthy controls. Genotyping was performed using sequence-specific primers.Results. The microarray analysis revealed HLA-DRB5 to be the only gene commonly up-regulated in patients with ILD compared with those without ILD in both comparison groups. High expression levels of HLA-DRB5 in SSc patients with ILD were confirmed by real-time quantitative PCR. The prevalence of HLA-DRB5 gene carriers increased in the SSc patients with ILD relative to those without ILD or to healthy controls in both cohorts. Among the four detected alleles, the HLA-DRB5*01:05 allele was significantly more frequent in SSc patients with ILD than in SSc patients without ILD or in healthy controls. These associations were confirmed in the second cohort.Conclusion. HLA-DRB5 was highly expressed in PBMCs from patients with SSc-related ILD. The HLA-DRB5*01:05 allele is a risk factor for ILD in patients with SSc. [ABSTRACT FROM PUBLISHER]