Rabbit antithymocyte globulin–induced serum sickness disease and human kidney graft survival

Autor: Gwénaëlle Evanno, Arnaud Nicot, Ludmilla Le Berre, Yohann Foucher, Stéphanie Castagnet, Jean Harb, Pavel Vesely, Sophie Brouard, Ondrej Viklicky, Juliette Rousse, Evelyn Ang, Apolline Salama, Magali Giral, Jean-Marie Bach, Hélène Perreault, Thomas Dejoie, Béatrice Charreau, Petra Hruba, Pierrick Guerif, Grégoire Couvrat-Desvergnes, Jean-Paul Soulillou, Marine Lorent
Přispěvatelé: Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Société d’Accélération du Transfert de Technologies Ouest Valorisation [Rennes, France], Xenothera [Nantes, France], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), CEITEC - Central European Institute of Technology [Brno, Czech Republic], Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Etablissement Français du Sang [Nantes], Labex Transplantex, the Natural Science and Engineering Research Council of Canada (RGPIN/170241) and Canadian Foundation for Innovation (22391), the Région Pays de la Loire., ANR-11-JSV1-0008,CSM (Composite Surrogate Marker),Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale(2011), European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Etablissement Français du Sang EFS [Nantes] (Laboratoire HLA), ANR: ANR-11-JSV1-0008-01, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Soulillou, Jean-Paul, Le Bihan, Sylvie, Jeunes Chercheuses et Jeunes Chercheurs - Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale - - CSM (Composite Surrogate Marker)2011 - ANR-11-JSV1-0008 - JCJC - VALID, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID
Rok vydání: 2015
Předmět:
Zdroj: Journal of Clinical Investigation
Journal of Clinical Investigation, 2015, 125 (12), pp.4655-4665. ⟨10.1172/JCI82267⟩
Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (12), pp.4655-4665. ⟨10.1172/JCI82267⟩
Journal of Clinical Investigation 12 (125), 4655-4665. (2015)
ISSN: 1558-8238
0021-9738
DOI: 10.1172/jci82267
Popis: Grégoire Couvrat-Desvergnes, Apolline Salama, and Ludmilla Le Berre contributed equally to this work.; International audience; BACKGROUND: Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.METHODS: We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.RESULTS: SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.CONCLUSION: In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.FUNDING: This study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.
Databáze: OpenAIRE
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