Longitudinal proteomics study of serum changes after allogeneic HSCT reveals potential markers of metabolic complications related to aGvHD

Abstract

Even though hematopoietic stem cell transplantation (HSCT) allows successful treatment for many malignant and non-malignant disorders, its curative potential remains limited by severe side effects, including infections and other transplant-related complications such as graft-versus-host disease (GvHD). This study examined changes in serum proteome via high-performance two-dimensional gel electrophoresis (2-DE) during HSCT to search for diagnostic biomarkers for post-HSCT complications. Longitudinal proteomic analysis revealed proteins related to metabolic complications and hemolytic anemia. Retinol-binding protein 4 (RBP4), a reliable marker of insulin resistance, was identified, and is possibly associated with the onset mechanism of acute graft-versus-host disease (aGvHD) and/or skin GvHD. Although the cause of insulin resistance is not fully understood, it is thought to be associated with adipocytes inflammation induced by RBP4, iron overload and hemolytic anemia after HSCT, as observed in this study. The present study has demonstrated that insulin resistance and metabolic complications could be immediate complications after transplantation and are associated with aGvHD. The biomarkers revealed in this study are promising tools to be used for improving the early diagnosis of HSCT-associated complications, especially aGvHD, possibly even before clinical manifestations.