Breathomics to monitor interstitial lung disease associated with systemic sclerosis.

Exhaled breath analysis, utilising VOCs, offers promise in identifying SSc-ILD patients, aiding targeted treatment. Further multicentric studies are crucial for validation and exploring longitudinal VOC changes for comprehensive disease management. https://bit.ly/4aKMYif.

High Prevalence of Myositis-Specific and Associated Antibodies in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time.

Plasma Dephosphorylated-Uncarboxylated Matrix Gla-Protein in Systemic Sclerosis Patients: Biomarker Potential for Vascular Calcification and Inflammation.

BACKGROUND: Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc's development, are the primary dp-ucMGP producers. This study assessed dp-ucMGP levels and initial CVD events in early-diagnosed SSc patients, investigating its potential as a CVD and all-cause mortality predictor over time. METHODS: In a cohort of 87 SSc patients (excluding those with pre-existing CVD or on dialysis), baseline dp-ucMGP levels were measured, along with cardiovascular risk factors. Validation involved assessing dp-ucMGP in a subset of treatment-naive SSc patients. RESULTS: A significantly elevated median dp-ucMGP level of 634 pmol/L (IQR 301) compared with healthy controls (dp-ucMGP < 393 pmol/L; p < 0.001) was observed. Validation in a treatment-naive SSc patient subset yielded similar results (median 589 pmol/L; IQR 370). During a median 10.5-year follow-up among 78 SSc patients, 33.3% experienced their first CVD event, independent of traditional risk factors. Elevated dp-ucMGP levels (>634 pmol/L) correlated with a higher risk of CVD and/or death (log-rank test: p < 0.01). CONCLUSIONS: In summary, dp-ucMGP emerges as a novel biomarker in SSc patients, with elevated levels indicating an increased risk of CVD and/or mortality in this population.

Vascular Remodeling in Pulmonary Arterial Hypertension: The Potential Involvement of Innate and Adaptive Immunity.

Pulmonary arterial hypertension (PAH) is a severe disease with high morbidity and mortality. Current therapies are mainly focused on vasodilative agents to improve prognosis. However, recent literature has shown the important interaction between immune cells and stromal vascular cells in the pathogenic modifications of the pulmonary vasculature. The immunological pathogenesis of PAH is known as a complex interplay between immune cells and vascular stromal cells, via direct contacts and/or their production of extra-cellular/diffusible factors such as cytokines, chemokines, and growth factors. These include, the B-cell-mast-cell axis, endothelium mediated fibroblast activation and subsequent M2 macrophage polarization, anti-endothelial cell antibodies and the versatile role of IL-6 on vascular cells. This review aims to outline the major pathophysiological changes in vascular cells caused by immunological mechanisms, leading to vascular remodeling, increased pulmonary vascular resistance and eventually PAH. Considering the underlying immunological mechanisms, these mechanisms may be key to halt progression of disease.