title: CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease.
abstract: Although graft-versus-host disease (GVHD) is a life-threatening complication of hematopoietic stem-cell transplantation (HSCT), its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8972-Da molecular mass (m/z) retained a discriminatory value in 2 diagnostic groups (GVHD and normal controls) with increased expression in the disease and decreased expression during cyclosporin A treatment, and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean +/- SE: 22.5 +/- 5.5 pg/mL, range: 12.6-48.0 pg/mL, n = 7). In sharp contrast, CCL8 was highly up-regulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean +/- SE: 165.0 +/- 39.8 pg/mL, n = 7). Strikingly, 2 patients with severe fatal GVHD had extremely high levels of CCL8 (333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.
authors.affiliation: Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hori
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Naishiro
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sohma
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sonoda
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mizue
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054412:Chemokine CCL8 / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry; D011070:Poly I-C / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D054412:Chemokine CCL8; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D016572:Cyclosporine; D011070:Poly I-C