Frequency of CD4+CD25hiFOXP3+ Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-Host-Disease

John M. Magenau, Xuemei Qin, Isao Tawara, Clare E. Rogers, Carrie Kitko, Matthew Schlough, Daniel Bickley, Thomas M. Braun, Pil Sang Jang, Kathleen P. Lowler, Dawn M. Jones, Sung W. Choi, Pavan Reddy, Shin Mineishi, John E. Levine, James L M Ferrara, Sophie Paczesny

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The relationship between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) in clinical allogeneic bone marrow transplantation (BMT) recipients is not well established. We conducted a prospective analysis of peripheral blood Tregs as determined by the frequency of CD4+CD25hiFOXP3+ lymphocytes in 215 BMT patients. Autologous BMT patients (N = 90) and allogeneic BMT patients without GVHD (N = 65) had similar Treg frequencies, whereas allogeneic patients with GVHD (N = 60) had Treg frequencies that were 40% less than those without GVHD. Treg frequencies decreased linearly with increasing grades of GVHD at onset, and correlated with eventual maximum grade of GVHD (P <001). In addition, frequency of Tregs at onset of GVHD predicted the response to GVHD treatment (P = 003). Patients with Treg frequencies less than the median had higher nonrelapse mortality (NRM) than patients with Tregs greater than the median, but experienced equivalent relapse mortality, resulting in an inferior survival at 2 years (38% versus 63%, P = 03). Treg frequency may therefore have important prognostic value as a biomarker of aGVHD.

Original languageEnglish (US)
Pages (from-to)907-914
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Graft vs Host Disease
Regulatory T-Lymphocytes
Biomarkers
Bone Marrow Transplantation
Homologous Transplantation
Mortality
Autologous Transplantation
Lymphocytes
Recurrence
Survival

Keywords

  • Acute graft-versus-host-disease
  • Allogeneic BMT
  • Biomarker
  • Regulatory T cells

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Frequency of CD4+CD25hiFOXP3+ Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-Host-Disease. / Magenau, John M.; Qin, Xuemei; Tawara, Isao; Rogers, Clare E.; Kitko, Carrie; Schlough, Matthew; Bickley, Daniel; Braun, Thomas M.; Jang, Pil Sang; Lowler, Kathleen P.; Jones, Dawn M.; Choi, Sung W.; Reddy, Pavan; Mineishi, Shin; Levine, John E.; Ferrara, James L M; Paczesny, Sophie.

In: Biology of Blood and Marrow Transplantation, Vol. 16, No. 7, 07.2010, p. 907-914.

Research output: Contribution to journalArticle

Magenau, JM, Qin, X, Tawara, I, Rogers, CE, Kitko, C, Schlough, M, Bickley, D, Braun, TM, Jang, PS, Lowler, KP, Jones, DM, Choi, SW, Reddy, P, Mineishi, S, Levine, JE, Ferrara, JLM & Paczesny, S 2010, 'Frequency of CD4+CD25hiFOXP3+ Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-Host-Disease', Biology of Blood and Marrow Transplantation, vol. 16, no. 7, pp. 907-914. https://doi.org/10.1016/j.bbmt.2010.02.026
Magenau, John M. ; Qin, Xuemei ; Tawara, Isao ; Rogers, Clare E. ; Kitko, Carrie ; Schlough, Matthew ; Bickley, Daniel ; Braun, Thomas M. ; Jang, Pil Sang ; Lowler, Kathleen P. ; Jones, Dawn M. ; Choi, Sung W. ; Reddy, Pavan ; Mineishi, Shin ; Levine, John E. ; Ferrara, James L M ; Paczesny, Sophie. / Frequency of CD4+CD25hiFOXP3+ Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-Host-Disease. In: Biology of Blood and Marrow Transplantation. 2010 ; Vol. 16, No. 7. pp. 907-914.
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abstract = "The relationship between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) in clinical allogeneic bone marrow transplantation (BMT) recipients is not well established. We conducted a prospective analysis of peripheral blood Tregs as determined by the frequency of CD4+CD25hiFOXP3+ lymphocytes in 215 BMT patients. Autologous BMT patients (N = 90) and allogeneic BMT patients without GVHD (N = 65) had similar Treg frequencies, whereas allogeneic patients with GVHD (N = 60) had Treg frequencies that were 40{\%} less than those without GVHD. Treg frequencies decreased linearly with increasing grades of GVHD at onset, and correlated with eventual maximum grade of GVHD (P <001). In addition, frequency of Tregs at onset of GVHD predicted the response to GVHD treatment (P = 003). Patients with Treg frequencies less than the median had higher nonrelapse mortality (NRM) than patients with Tregs greater than the median, but experienced equivalent relapse mortality, resulting in an inferior survival at 2 years (38{\%} versus 63{\%}, P = 03). Treg frequency may therefore have important prognostic value as a biomarker of aGVHD.",
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