Novel biomarker for pulmonary vascular disease in systemic sclerosis patients

Clin Exp Rheumatol. 2022 Oct;40(10):1956-1963. doi: 10.55563/clinexprheumatol/0exnav. Epub 2022 Apr 29.


Objectives: In systemic sclerosis (SSc) patients, pulmonary arterial hypertension (PAH), which is preceded by pulmonary vascular disease (PVD), is one the of major causes of morbidity and mortality. Given the higher risk of PAH among anti-CENP antibodies (ACA)+ patients, we previously characterised a subset of ACA+ patients, based on a differential reactivity of their ACA with the phage clone (pc4.2)-expressing peptide 4.2 (p4.2). There was a considerably greater prevalence of a low diffusing lung capacity for carbon monoxide (DLCO), an expression of PVD, among patients with high anti-pc4.2 Ab levels. Here we examine whether a similar clinical subgroup can be identified within a larger cohort of ACA+ patients, using the synthetic p4.2.

Methods: Clinical data and serum samples were collected from 134 ACA+ patients. Sera were screened for reactivity with p4.2 by indirect ELISA. Statistical analyses were performed to define any associations between anti-p4.2 Ab levels and PVD.

Results: Kendall's analysis showed that anti-p4.2 Ab were directly associated with both a reduced DLCO and the presence of pulmonary fibrosis (PF). These associations were confirmed by Fisher's exact test. At multivariate analysis, anti-p4.2 Ab was associated to DLCO<70, DLCO≤60, and PF. Moreover, multivariable analysis showed that only the association of anti-p4.2 Ab with DLCO<70, and not with DLCO≤60, was independent of PF.

Conclusions: Anti-p4.2 Ab are able to identify SSc patients at high risk of developing PVD even in the absence of PF. Patients with high anti-p4.2 Ab levels should be strictly monitored for PVD onset and eventually PAH.

MeSH terms

  • Biomarkers
  • Carbon Monoxide / metabolism
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / etiology
  • Pulmonary Fibrosis*
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / diagnosis
  • Vascular Diseases* / etiology


  • Carbon Monoxide
  • Biomarkers