title: YKL-40 identified by proteomic analysis as a biomarker of sepsis.
abstract: To investigate changes in protein expression by proteomic analysis in the sera of patients with sepsis and to identify new biomarkers of sepsis. A total of 45 consecutive patients with severe sepsis or septic shock (sepsis group), 22 healthy volunteers, and 23 patients undergoing off-pump coronary artery bypass grafting (control group). Serum samples from eight patients of each group underwent proteomic analysis involving removal of 12 major proteins and subsequent reversed-phase high-performance liquid chromatography fractionation and one-dimensional electrophoresis. The intensity of 41 bands (with 12 proteins identified) increased and that of 42 bands (with 22 proteins identified) decreased in the sepsis group. Results of proteomic analysis successfully validated by Western blotting and/or enzyme-linked immunosorbent assay for three proteins (YKL-40, lipocalin 2, and S100A9) increased in the sepsis group as well as two proteins (retinol-binding protein, vitamin D-binding protein) decreased. Serum YKL-40 levels (sYKL-40) on intensive care unit (ICU) admission were assessed by enzyme-linked immunosorbent assay between the two groups; resulting YKL-40 was significantly higher in the sepsis group (P < 0.001). Furthermore, sYKL-40 on ICU admission was significantly higher in patients with positive blood culture (P < 0.005), patients with septic shock (P < 0.05), and patients requiring continuous hemodiafiltration (P < 0.05) or hydrocortisone replacement therapy (P < 0.005) during subsequent treatment. A positive correlation between sYKL-40 and blood IL-6 level on ICU admission was noted in the sepsis group (r = 0.465, P < 0.01). YKL-40 identified by proteomic analysis is considered as a biomarker of sepsis. However, further investigation is needed to clarify its roles and clinical usefulness as a biomarker.
authors.affiliation: Department of Emergency and Critical Care Medicine, Chiba University, Graduate School of Medicine, Chiba, Japan. hat@shogo.com
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hattori
authors.forename: Shigeto
authors.initials: S
authors.lastname: Oda
authors.forename: Tomohito
authors.initials: T
authors.lastname: Sadahiro
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Abe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shinozaki
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sogawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirasawa
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D054392:Adipokines; D000368:Aged; D015153:Blotting, Western; D040502:Calgranulin B / Q000378:metabolism; D000071451:Chitinase-3-Like Protein 1; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D037102:Lectins / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D012772:Shock, Septic / Q000097:blood / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D054392:Adipokines; C084533:CHI3L1 protein, human; D040502:Calgranulin B; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D015850:Interleukin-6; C489506:LCN2 protein, human; D037102:Lectins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012177:Retinol-Binding Proteins; D014809:Vitamin D-Binding Protein