Longitudinal plasma proteome profiling after allogeneic hematopoietic stem cell transplantation: heterogeneous development and associations with acute GvHD.

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for malignant and non-malignant hematopoietic diseases, but the development of acute graft-versus-host disease (GvHD) caused by donor immune cell-mediated inflammation and destruction of host tissues poses a significant challenge. It remains difficult to predict whether and when patients will develop acute GvHD. Here, we used mass-spectrometry (MS)-based proteomics to identify plasma proteins associated with allogenic HSCT and acute GvHD development. In this study, we analyzed longitudinal plasma samples at baseline (pre-HSCT), 1, 3, 6, and 12 months post-HSCT from 10 allogeneic HSCT recipients, 7 of whom developed acute GvHD, and 5 healthy donors. As expected, significant differences between the plasma proteomes of allogeneic HSCT recipients and healthy donors were found. The most pronounced differences were observed 3 months post-HSCT, with four proteins (C4A, FTL, GNPTG, S100A9) that were altered before allogeneic HSCT and remained altered up to 12 months post-HSCT compared to healthy donors. Three other proteins (VWF, RNASE4, B2M) showed alterations only after transplantation. Moreover, co-expression analysis revealed an association between inflammation-related proteins (ITIH3, ITLN1, COLEC11, SERPING1, SERPIND1 and IgG) and acute GvHD grade. Together, we demonstrate how plasma proteomic profiling can support the monitoring of acute GvHD in allogeneic HSCT recipients.