Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Growth Differentiation Factor-15 (GDF-15), and Soluble C5b-9 (sC5b-9) Levels Are Significantly Associated with Endothelial Injury Indices in CAR-T Cell Recipients

• Published in: International journal of molecular sciences 2024-10, Vol.25 (20), p.11028
• Main Authors: Gavriilaki, Eleni, Demosthenous, Christos, Evangelidis, Paschalis, Bousiou, Zoi, Batsis, Ioannis, Vardi, Anna, Mallouri, Despina, Koravou, Eudoxia-Evaggelia, Spyridis, Nikolaos, Panteliadou, Alkistis, Karavalakis, Georgios, Masmanidou, Marianna, Touloumenidou, Tasoula, Papalexandri, Apostolia, Poziopoulos, Christos, Yannaki, Evangelia, Sakellari, Ioanna, Politou, Marianna, Papassotiriou, Ioannis
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - blood; Disease; FDA approval; Female; Growth Differentiation Factor 15 - blood; Growth Differentiation Factor 15 - metabolism; Hematology; Humans; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphoma; Male; Middle Aged; Mortality; Multivariate analysis; Pathophysiology; Receptors, Urokinase Plasminogen Activator - blood; Receptors, Urokinase Plasminogen Activator - metabolism; Regression analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252011028

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients' group compared to the healthy control group ( < 0.001, in all comparisons). SuPAR levels at baseline were associated with the m-EASIX scores calculated at the same time point ( = 0.020), while suPAR and GDF-15 concentrations were correlated with EASIX scores at day 14 post-infusion ( < 0.001 in both comparisons). Moreover, sC5b-9 levels were correlated with the s-EASIX scores at infusion ( = 0.008) and the EASIX scores at day 14 ( = 0.005). In our study, sC5b9, suPAR, and GDF-15 levels were found to reflect endothelial injury in CAR-T cell recipients.