Frequency of CD4 + CD25 hi FOXP3 + Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-Versus-Host Disease.

Abstract 514 JMM and XQ contributed equally to this work . Regulatory T cells (Treg) play an important role in the maintenance of tolerance after bone marrow transplantation (BMT) in experimental models. However, the relationship between Treg and acute graft-versus-host disease (GVHD) in allogeneic BMT recipients is not well established. We conducted a prospective analysis of Treg frequency in 215 BMT patients (125 allogeneic, 90 autologous) at the University of Michigan. Fresh peripheral blood samples were acquired prior to therapy within 24 hours of GVHD onset and at equivalent time points in patients without GVHD. Treg frequency was measured in triplicate by three color cytometry analysis to determine the frequency of CD4 + CD25 hi FOXP3 + cells within total lymphocytes. There were no significant differences between patients with and without GVHD for median age, nonmalignant disease, conditioning intensity, and median day of sample acquisition. Recipients of grafts from donors who were not family members or who were not HLA-matched were overrepresented in the GVHD group. Autologous BMT patients (N=90) and allogeneic BMT patients without GVHD (N=65) had the same mean Treg frequency (1.09% ± 0.10 vs. 1.09% ± 0.11, p = 0.54), showing that the use of calcineurin inhibitors did not affect Treg frequency. Patients with GVHD (N=60) had 40% fewer Treg (0.66% ± 0.07, p + CD25 hi FOXP3 + Tregs at onset of GVHD correlates with GVHD severity, eventual maximum grade and NRM. Treg frequency thus has important diagnostic and prognostic value as biomarker for acute GVHD. Disclosures: No relevant conflicts of interest to declare.