Complete donor chimerism is a prerequisite for the effect of Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) on acute graft-versus-host disease

Predicted indirectly recognizable HLA epitopes (PIRCHE) computationally predict donor T-cell recognition of mismatched-HLA derived peptides following allogeneic haematopoietic stem-cell transplantation (allo-HSCT), as is evidenced by the correlation between presence of HLA-DPB1-derived PIRCHE and the occurrence of graft-vs.-host disease (GVHD). Complete donor T-cell chimerism associates with an increased GVHD risk compared to mixed patient and donor chimerism. If the correlation between the presence of PIRCHE and GVHD occurrence is indeed mediated by donor T cells, the presence of donor T cells should be required to observe such a correlation. This study was initiated to investigate whether the effect of PIRCHE is different in patients with complete chimerism compared to those with mixed chimerism. Indeed, the correlation between PIRCHE and GVHD is present in patients with complete chimerism, whereas it is absent in those with mixed chimerism. The data presented here suggest that chimerism status is important for the detection of potential GVHD epitopes.