Front Immunol

Introduction: Extracorporeal photopheresis (ECP) is a safe, effective treatment for steroid-refractory acute GVHD (SR-aGVHD). Endothelial damage is a pathological substrate of aGVHD.

Methods: Endothelial damage biomarkers were measured in SR-aGVHD patients' plasma before (PRE) and 1-month after initiating ECP as second-line therapy to explore differences by treatment response. ECP-treated SR-aGVHD patients (n=35) were classified into good (GR; n=18) and poor (PR; n=17) responders. Endothelial activation biomarkers (soluble Vascular Cell Adhesion Molecule-1, sVCAM-1; von Willebrand Factor, VWF; thrombomodulin, TM; soluble TNF receptor 1, sTNFR1; angiopoietin 2; ANG2); GVHD markers (suppression tumorigenicity 2, ST2; regenerating islet-derived 3-alpha, REG3alpha; T-cell immunoglobulinmucin-3, TIM3); soluble C5b9 (sC5b9), for complement activation; and circulating dsDNA, for neutrophil extracellular traps (NETs), were analyzed. The endothelial activation and stress index (EASIX) and C-reactive protein were evaluated.

Results: Before ECP, endothelial damage biomarkers were elevated in all patients, with no significant differences between GR and PR. After 1-month, increased levels of REG3alpha and sC5b9, and decreased levels of TIM3, were observed in samples from PR. A panel combining 5 biomarkers (ST2, VWF, NETs, TIM3, ANG2) could identify GR after 1-month on ECP (likelihood ratio 2.0) and predict ECP response.

Discussion: We propose a simplified endothelial damage biomarker panel capturing early biological signals associated with response to ECP in SR-aGVHD patients.