title: Correlation of donor-derived keratinocytes and severity of graft-versus-host disease (GVHD) in epidermis.
abstract: Recent reports suggest that bone marrow might serve as a source of skin progenitor cells. Graft-versus-host disease (GVHD) is a systemic disease that involves the skin, the liver, and the gastrointestinal tract, and contributes to transplant-related morbidity and mortality. To evaluate whether donor-derived bone marrow cells participated in its pathophysiology, we correlated the severity of GVHD in skin from sex-mismatched recipients with the percentage of donor-derived keratinocytes using fluorescence in situ hybridization (FISH) for detecting the Y chromosome. Y-positive signals were observed in female epidermis in both keratinocytes and lymphocytes. These results support the notion that donor-derived hematopoietic stem cells may contain pluripotent stem cells. Furthermore, there was a strong correlation between the frequency of Y-positive keratinocytes and the histopathologic grade of GVHD (p = 0.004), as well as with the number of Y-positive lymphocytes infiltrating the epidermis (p = 0.005), suggesting a role for donor-derived keratinocytes in the pathophysiology of GVHD. However, no clusters of Y-positive keratinocytes were found in the epidermis, and no correlation was observed between the number of Y-positive keratinocytes and time course of GVHD after transplantation. We hypothesize that donor-derived stem cells may play a role in the regeneration of damaged keratinocytes in GVHD.
authors.affiliation: Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Matsuu
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shichijo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekine
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002452:Cell Count; D041322:Chromosomes, Human, Y / Q000235:genetics; D004817:Epidermis / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D006087:Graft vs Host Reaction; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015603:Keratinocytes / Q000473:pathology*; D008875:Middle Aged; D039904:Pluripotent Stem Cells / Q000473:pathology / Q000502:physiology; D012871:Skin Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D014019:Tissue Donors