International Journal of Molecular Sciences (Dec 2023)

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients

  • Eleni Gavriilaki,
  • Zoi Bousiou,
  • Ioannis Batsis,
  • Anna Vardi,
  • Despina Mallouri,
  • Evaggelia-Evdoxia Koravou,
  • Georgia Konstantinidou,
  • Nikolaos Spyridis,
  • Georgios Karavalakis,
  • Foteini Noli,
  • Vasileios Patriarcheas,
  • Marianna Masmanidou,
  • Tasoula Touloumenidou,
  • Apostolia Papalexandri,
  • Christos Poziopoulos,
  • Evangelia Yannaki,
  • Ioanna Sakellari,
  • Marianna Politou,
  • Ioannis Papassotiriou

DOI
https://doi.org/10.3390/ijms25010231
Journal volume & issue
Vol. 25, no. 1
p. 231

Abstract

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Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) and graft-versus-host disease (GvHD) represent life-threatening syndromes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both conditions, endothelial dysfunction is a common denominator, and development of relevant biomarkers is of high importance for both diagnosis and prognosis. Despite the fact that soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings, their role in HSCT-related complications remains unexplored. In this context, we used immunoenzymatic methods to measure suPAR and GDF-15 levels in HSCT-TMA, acute and/or chronic GVHD, control HSCT recipients, and apparently healthy individuals of similar age and gender. We found considerably greater SuPAR and GDF-15 levels in HSCT-TMA and GVHD patients compared to allo-HSCT and healthy patients. Both GDF-15 and suPAR concentrations were linked to EASIX at day 100 and last follow-up. SuPAR was associated with creatinine and platelets at day 100 and last follow-up, while GDF-15 was associated only with platelets, suggesting that laboratory values do not drive EASIX. SuPAR, but not GDF-15, was related to soluble C5b-9 levels, a sign of increased HSCT-TMA risk. Our study shows for the first time that suPAR and GDF-15 indicate endothelial damage in allo-HSCT recipients. Rigorous validation of these biomarkers in many cohorts may provide utility for their usefulness in identifying and stratifying allo-HSCT recipients with endothelial cell impairment.

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