Increased gene expression of chemokine receptors is correlated with acute graft-versus-host disease after allogeneic stem cell transplantation

Abstract

Acute graft-versus-host disease (GVHD) is still a major complication after allogeneic stem cell transplantation. It is initiated by infiltrating donor T cells specific against the host antigens. Because T-cell migration is largely controlled by the expression of chemokines and chemokine receptors, we investigated the relation of acute GVHD and chemokine receptor expression in peripheral blood in 50 patients after allogeneic stem cell transplantation. The gene expression of the chemokine receptors CCR1, CCR2, CCR5, and CXCR3 was monitored by using quantitative real-time polymerase chain reaction. Among the 36 patients diagnosed with acute GVHD, 10 developed a second episode of acute GVHD. Therefore, gene-expression levels could be analyzed in 46 occasions of acute GVHD. When all 4 markers were evaluated at the same time, increased gene-expression levels of at least 1 of the 4 markers were seen in 44 of 46 episodes of acute GVHD. The median increase of the 4 markers ranged from 3x to 12x in connection with acute GVHD. It is interesting to note that we saw increasing gene-expression levels a few days before acute GVHD was diagnosed clinically at 17, 15, 22, and 19 occasions for CCR5, CXCR3, CCR1, and CCR2, respectively. The median number of days before diagnosis ranged from 3 to 5. Although they are not specific for acute GVHD, quantitative monitoring of the gene expression of chemokine receptors may be a valuable molecular method to monitor and diagnose acute GVHD.