TD-GC×GC-HRTOFMS for Breath Profiling of Systemic Sclerosis

in Proceedings (2021)

A new nucleosomic-based model to identify and diagnose SSc-ILD

in Clinical Epigenetics (2020), 12(1), 124

BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the ... [more ▼]

BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the evolution of the lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Nucleosomes are stable DNA/protein complexes that are shed into the blood stream making them ideal candidates for biomarkers. METHODS: We studied circulating cell-free nucleosomes (cf-nucleosomes) in SSc patients, 31 with ILD (SSc-ILD) and 67 without ILD. We analyzed plasma levels for cf-nucleosomes and investigated whether global circulating nucleosome levels in association with or without other biomarkers of interest for systemic sclerosis or lung fibrosis (e.g., serum growth factors: IGFBP-1 and the MMP enzyme: MMP-9), could be suitable potential biomarkers for the correct identification of SSc-ILD disease. RESULTS: We found that H3.1 nucleosome levels were significantly higher in patients with SSc-ILD compared SSc patients without ILD (p < 0.05) and levels of MMP-9 were significantly increased in patients with SSc-ILD compared to SSc patients without ILD (p < 0.05). Conversely, IGFBP-1 was significantly reduced in patients with SSc-ILD compared to SSc without ILD (p < 0.001). The combination of cf-nucleosomes H3.1 coupled to MMP-9 and IGFBP-1 increased the sensitivity for the differential detection of SSc-ILD. High levels of accuracy were reached with this combined model: its performances are strong with 68.4% of positive predictive value and 77.2% of negative predictive value for 90% of specificity. With our model, we identified a significant negative correlation with FVC % pred (r = -0.22) and TLC % pred (r = -0.31). The value of our model at T1 (baseline) has a predictive power over the Rodnan score at T2 (after 6-18 months), showed by a significant linear regression with R2 = 19% (p = 0.013). We identified in the sole group of SSc-ILD patients a significant linear regression with a R2 = 54.4% with the variation of DLCO between T1 and T2 (p < 0.05). CONCLUSION: In our study, we identified a new blood-based model with nucleosomic biomarker in order to diagnose SSc-ILD in a SSc cohort. This model is correlated with TLC and FVC at baseline and predictive of the skin evolution and the DLCO. Further longitudinal exploration studies should be performed in order to evaluate the potential of such diagnostic and predictive model. [less ▲]

Cardiovascular outcome in systemic sclerosis.

in Acta Cardiologica (2015), 70(5), 554-63

OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC ... [more ▼]

OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS: We prospectively enrolled 65 patients with SSc (age 54+/-14 years, 30% female) followed in CHU Sart-Tilman, Liege, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS: EIPH was present in 21 patients. During FU (27+/-18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63+/-14 vs 52+/-13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30+/-6 vs 24+/-6; P=0.007 and 57+/-13 vs 44+/-13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112+/-106 vs 26+/-19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ss=2.4+/-1.1; P=0.03), EIPH (ss=2.30+/-1.13; P=0.04), FUPH (ss=0.24+/-0.09; P=0.01 and ss=3.52+/-1.16; P=0.002, respectively;) and BNP (ss=0.08+/-0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION: Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc. [less ▲]

The management of systemic lupus erythematosus with biological therapies

in Revue Médicale Suisse (2013), 9(395), 1507-11