Activated circulating dendritic cells after hematopoietic stem cell transplantation predict acute graft-versus-host disease

Background. Dendritic cells (DC) are central to the development of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT). We hypothesized that DC activation status determines the severity of GVHD and that activated DC may be detected in the circulation prior to clinical presentation of GVHD. Methods. Following transplant, blood samples were obtained twice weekly from alloHSCT patients. Myeloid (CD11c(+)) and plasmacytoid (CD123(hi)) DC were enumerated by flow cytometry, and activated myeloid DC were identified using the CMRF-44 monoclonal antibody. Results. Of 40 alloHSCT patients, 26 developed acute GVHD. Severity of GVHD was associated with low total blood DC counts (P=0.007) and with low myeloid and plasmacytoid DC numbers (P=0.015 and 0.003). The CMRF-44 antigen was expressed on blood CD11c(+) DC in all cases prior to GVHD onset, whereas of the 14 patients without GVHD, seven had no CMRF-44(+) CD11c(+) DC. Patients with CMRF-44(+) CD11c(+) DC in more than 20% of samples were more likely to subsequently develop acute GVHD (P=0.001, odds ratio=37.1), while patients who developed grade 2-4 GVHD had prior higher percentages of CMRF-44(+) CD11c(+) DC compared to grade 0-1 GVHD patients (P=0.001). CMRF-44 expression on > 7.9% CD11c(+) DC predicted for subsequent development of GVHD with a sensitivity of 87.5% and specificity of 79.2%. Conclusions. Activation status, as assessed by CMRF-44 antigen expression, of blood CD11c(+) DC is highly associated with acute GVHD and these cells may be targets for therapeutic intervention.