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  4. Beneficial immune effects of myeloid-related proteins in kidney transplant rejection
 
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2016
Journal Article
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. The authors find an association between levels of S100 calcium-binding proteins A8 and A9 during acute kidney transplant rejection with graft outcome, and that these myeloid cell-expressed proteins have immunoregulatory effects toward T cells.
Author(s)
Rekers, Niels V.
Leiden University Medical Center
Bajema, Ingeborg M.
Leiden University Medical Center
Mallat, Marko J.K.
Leiden University Medical Center
Petersen, Beatrix
Universität Münster
Anholts, Jaqueline D.
Leiden University Medical Center
Swings, Godelieve M.
Leiden University Medical Center
Miert, Paula P. van
Leiden University Medical Center
Kerkhoff, Claus
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
Roth, Johannes
Universität Münster
Popp, David
Universität Münster
Groningen, Marian C. van
Erasmus Medical Center, Rotterdam
Baeten, Dominique L.
University of Amsterdam
Goemaere, Natascha N.
Erasmus Medical Center, Rotterdam
Kraaij, Marina D.
Leiden University Medical Center
Zandbergen, Malu
Leiden University Medical Center
Heidt, S.
Leiden University Medical Center
Kooten, Cees van
Leiden University Medical Center
Fijter, Johan W. de
Leiden University Medical Center
Claas, Frans H.J.
Leiden University Mediical Center
Eikmanns, Michael
Leiden University Medical Center
Journal
American journal of transplantation  
Open Access
DOI
10.1111/ajt.13634
Additional full text version
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Language
English
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
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