E-selectin combined with soluble CD44 as predictors of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Abstract

Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the mainly curable treatment options in children with high-risk malignancies, bone marrow failure diseases and inherited metabolic diseases. Acute graft-versus-host disease (aGVHD) accompanied with series of serious complications are the most severe obstacle of allo-HSCT because the early and accurate diagnostic markers and effective treatment are still lacked. Non-organ-specific injury induced activated endothelial cells and tissue integrity biomarkers may have higher specificity for the occurrence and development of aGVHD. Methods The blood from 52 pediatric patients who underwent allo-HSCT including 16 recipients with aGVHD and 36 recipients without aGVHD were collected to check the level of adhesion molecules. The vitro experiments, transwell experiments, and aGVHD mouse model are used to verify the effects of E-selectin in the occurrence and development of aGVHD. Results We found that E-selectin secreted by endothelial cells was remarkably increased while the level of soluble CD44, a widely distributed tissue structure molecule, was significantly decreased in aGVHD patients. The level of E-selectin was negatively correlated with the soluble CD44 and associated with the severity of the aGVHD. After that, the vitro experiments suggested the elevated E-selectin could recruit immune cells that result in a series of inflammatory response and tissue injury. The aGVHD mouse model revealed that the level of E-selectin in the intestine occurred aGVHD was obviously increased than that without aGVHD. The expression level of CD44 in organs was related to the incidence of organ aGVHD. More importantly, the area under the ROC curve (AUC) of E-selectin and CD44 can reach 0.85 indicating that these two parameters have strong prediction ability of aGVHD. Conclusions E-selectin and CD44 could play an important role in the occurrence and development of aGVHD. E-selectin combined with soluble CD44 could act as efficient biomarkers for the diagnosis of aGVHD.