title: Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA-mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD.
abstract: Acute GVHD (aGVHD) is a major obstacle to allogeneic hematopoietic SCT (alloHSCT). Although it is thought that aGVHD is initiated in secondary lymphoid organs at a very early stage of alloHSCT, whether CD4(+)FOXP3(+) regulatory T-cells (Tregs) have an impact on aGVHD development during this period remains unclear. Here, we measured Tregs in peripheral blood as early as possible after HLA-mismatched alloHSCT, and assessed the incidence of aGVHD. Flow cytometric analyses revealed that at the second week after HSCT, patients with aGVHD had significantly (P=0.018) lower Treg:CD4(+)T-cell ratios than those without aGVHD. As these differences were seen before the development of aGVHD, these ratios can predict the incidence of aGVHD. The cumulative incidence of aGVHD in patients with ratios of <9% was significantly higher than that in patients with ratios of 9% (P=0.0082, log-rank test). Additionally, the specific ratio of Tregs:CD4(+)T-cells was the most significant value among all other possible lymphocyte-associated ratios and absolute cell counts. These findings suggest that the ratio of Tregs:CD4(+)T-cells at the second week post HLA-mismatched alloHSCT might be a potent predictor of aGVHD in these patients. The practical efficacy of this finding should be verified in further interventional studies.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. fujioka@hyo-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Fujioka
authors.forename: H
authors.initials: H
authors.lastname: Tamaki
authors.forename: K
authors.initials: K
authors.lastname: Ikegame
authors.forename: S
authors.initials: S
authors.lastname: Yoshihara
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Kaida
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: J
authors.initials: J
authors.lastname: Nakata
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Soma
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D064591:Allografts; D018791:CD4 Lymphocyte Count; D005260:Female; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens