title: Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.
abstract: Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: N V
authors.initials: NV
authors.lastname: Rekers
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: I M
authors.initials: IM
authors.lastname: Bajema
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M J K
authors.initials: MJ
authors.lastname: Mallat
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany.|Primate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Petersen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J D H
authors.initials: JD
authors.lastname: Anholts
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: G M J S
authors.initials: GM
authors.lastname: Swings
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P P M C
authors.initials: PP
authors.lastname: van Miert
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Department of Immunology, Rostock, Germany.|Department of Biomedical Sciences, University of Osnabrück, Osnabrück, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kerkhoff
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Roth
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Popp
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: van Groningen
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Baeten
authors.affiliation: Department of Pathology, Maasstad Hospital, Rotterdam, the Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Goemaere
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M D
authors.initials: MD
authors.lastname: Kraaij
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Zandbergen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Heidt
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Eikmans
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000276:immunology / Q000378:metabolism*; D040502:Calgranulin B / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D011379:Prognosis; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B