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* Institut National de la Santé et de la Recherche Médicale (INSERM), U662, Paris, France;
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Nephrology Unit Paris, France;
Université Paris 7, Institut Universitaire d’Hématologie, Paris, France;
AP-HP, Hôpital Saint-Louis, Centre d’Investigations Biomédicales "H-O-G", Paris, France;
¶ AP-HP, Hôpital Saint-Louis, Hematology Unit, Paris, France;
|| AP-HP, Hôpital Bichat, Nephrology Unit, Paris, France;
# Centre Hospitalier F. H. Manhes, Fleury Merogis, France;
** Clinique du Petit Colmoulins, Harfleur, France; and
Hôpital Saint-André, Metz, France
To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 The Imagery Department at the Institut Universitaire d’Hématologie is supported by grants from the Conseil Régional d’Ile de France and the Ministère de la Recherche. We also thank the Association pour l’Utilisation du Rein Artificiel (AURA; Paris, France), Astellas Pharma (Levallois Perret, France), Meditor (Hoenheim, France), and Canceropole Ile de France for their financial support.
2 M.-N.P. and J.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Marie-Noelle Peraldi, Department of Nephrology and Transplantation, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France. E-mail address: marie-noelle.peraldi{at}sls.aphp.fr
4 Abbreviations used in this paper: ESRD, end-stage renal disease; ROS, reactive oxygen species; MICA, MHC class I-related chain A; sMICA, soluble MICA; HD, healthy donors; rMFI, relative mean fluorescence intensity; GO, glucose oxidase.
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