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

Author:

Gavriilaki Eleni1ORCID,Bousiou Zoi2,Batsis Ioannis2,Vardi Anna2,Mallouri Despina2,Koravou Evaggelia-Evdoxia2,Konstantinidou Georgia2,Spyridis Nikolaos2,Karavalakis Georgios2,Noli Foteini2,Patriarcheas Vasileios2,Masmanidou Marianna2,Touloumenidou Tasoula2,Papalexandri Apostolia2,Poziopoulos Christos3,Yannaki Evangelia2,Sakellari Ioanna2,Politou Marianna4,Papassotiriou Ioannis5ORCID

Affiliation:

1. Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece

2. BMT Unit, Hematology Department, George Papanicolaou General Hospital, 57010 Thessaloniki, Greece

3. Department of Hematology, Metropolitan Hospital, Neo Faliro, 18547 Athens, Greece

4. Hematology Laboratory-Blood Bank, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

5. First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece

Abstract

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.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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