Lysyl oxidase-a possible role in systemic sclerosis-associated pulmonary hypertension: A multicentre study

Zahava Vadasz, Alexandra Balbir Gurman, Pierluigi Meroni, Dominique Farge, Yair Levi, Francesca Ingegnoli, Yolada Braun-Moscovici, Itzhak Rosner, Gleb Slobodin, Michael Rozenbaum, Nizar Jiries, Lisa Kaly, Nina Boulman, Karina Zilber, Shira Ginsberg, Abid Awisat, Yair Goldberg, Michael Lurie, Maria Rosa Ghigna, Christophe GuignabertMarc Humbert, Doron Rimar

Research output: Contribution to journalArticlepeer-review


Objective: Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. Methods: A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls. LOX serum levels were determined by ELISA. Five lung and 12 skin biopsies from SSc patients were stained for LOX and compared with controls. Results: Serum levels of LOX in SSc were significantly higher than in VEDOSS, PRP and healthy controls (P < 0.001). LOX inversely correlated with the diffusing capacity of the lung for carbon monoxide diffusing capacity (DLCO) in diffuse SSc (r =-0.376, P = 0.02). Patients with moderate to severe estimated systolic PAH had higher LOX levels (P < 0.01). Lung biopsies demonstrated intense LOX staining in SSc patients with PAH that was predominantly located in the endothelium of the remodelled pulmonary vessels. Conclusion: Serum LOX levels are increased in established SSc and inversely correlate with the DLCO. LOX is elevated in patients with moderate to severe PAH and is located in the proliferating endothelium in lung arterioles, suggesting a possible role for LOX in SSc-associated PAH.

Original languageEnglish
Pages (from-to)1547-1555
Number of pages9
Issue number9
StatePublished - 1 Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s).


  • biomarkers
  • fibrosis
  • lysyl oxidase
  • pulmonary arterial hypertension
  • systemic sclerosis
  • vasculopathy

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Rheumatology


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