BACKGROUND:

interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with SSc and combined PH and ILD (SSc?PH-ILD) generally have a poor prognosis. Predictors of survival are lacking in patients with SSc-PH-ILD.

OBJECTIVE:

To identify specific plasma protein expression patterns associated with survival in patients with SSc-PH-ILD.

MATERIALS AND METHODS:

Post-hoc analysis of a prospective multicenter French study in patients with PH-ILD. An untargeted proteomic analysis using mass spectrometry was performed to identify plasma protein changes associated with long-term overall survival in patients with SSc-PH-ILD.

RESULTS:

Thirty-two patients were included, of whom 13 died during follow-up (median survival: 2327 days). At baseline, survivors had less severe hemodynamic impairment (pulmonary vascular resistance of 4.4 Wood Units [IQR 3 - 5.2] vs. 6.2 Wood Units [IQR 4.2 - 10.7]) and higher carbon monoxide diffusing capacity (median 39% [IQR 35% - 44%] vs. 25% [IQR 22% - 30.5%]), than the 13 patients who died. Seven proteins, associated with haemostasis and fibrosis, were differentially expressed according to patients? survival. In the survivor group, two proteins were increased (ADAMTS13, SERPIND1) and five were decreased (PTGDS, OLFM1, C7, IGFBP7, FBN1) compared to the non-survivor groups.

CONCLUSION:

The prognosis of SSc-PH-ILD patients is poor. We found 7 plasma proteins (involved in haemostasis and fibrosis pathways) associated with survival. These potential biomarkers may be good candidates to prognostic enrichment.