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 (CD123hi) 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.
Lau
Jenny
J
1Westmead Millenium Institute, University of Sydney, Westmead Hospital, Sydney, Australia.
Sartor
Mary
M
Bradstock
Kenneth F
KF
Vuckovic
Slavica
S
Munster
David J
DJ
Hart
Derek N J
DN
D000328:Adult; D001794:Blood Pressure; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000145:classification / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D011237:Predictive Value of Tests; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
D005395:Fish Oils; D007166:Immunosuppressive Agents