title: Circulating endothelial progenitor cells decreased in patients with sclerodermatous chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is a common late complication of allogeneic stem cell transplantation (allo-SCT). Some cGVHD patients develop skin lesions, and the skin lesions in sclerodermatous cGVHD (s-cGVHD) patients resemble those in progressive systemic sclerosis (PSS), which is characterized by impaired production of circulating endothelial progenitor cells (EPCs). We investigated, retrospectively, whether low EPC production may promote the development of sclerodermatous lesions in cGVHD. Peripheral blood (PB) was obtained from 14 healthy volunteers and 27 allo-SCT patients. Five patients developed s-cGVHD. CD34(+) cells were purified by using the magnetic cell-sorting separation system, and the CD34(+)/CD133(+)/vascular endothelial growth factor (VEGF) receptor-2(+) EPCs were quantified. The endothelial cell colony-formation potential was evaluated. Serum VEGF and basic fibroblast growth factor (b-FGF) concentrations were measured by ELISA. The s-cGVHD patients had significantly lower median circulating EPCs frequencies than non-s-cGVHD patients or control (145 of 20 mL [interquartial range-IQR 107-193] versus 1083.5 [IQR 669.3-2151]; P = .0023, and versus 1530.5 [IQR 961.3-2158]; P = .0012, respectively). They also had impaired median endothelial-forming ability compared to non-s-cGVHD patients or controls (3.8 [IQR 1.0-4.3] versus 12.8 [IQR 8.8-28.8], and versus 26.4 [IQR 23.6-30.6], respectively; P = .0012). Their VEGF and b-FGF serum levels were also higher than in controls. In conclusion, s-cGVHD patients show findings consistent with those seen in PSS with impaired vasculogenesis that may limit blood perfusion and may contribute to the development of sclerodermatous lesions.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Shimura
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Hitoji
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D002908:Chronic Disease; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D045745:Scleroderma, Limited / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34