Quantitative and qualitative changes in anti‐Neu5Gc antibody response following rabbit anti‐thymocyte IgG induction in kidney allograft recipients
2019
Rousse, Juliette | Salama, Apolline | Leviatan Ben-Arye, Shani | Hruba, Petra | Slatinska, Janka | Evanno, Gwénaëlle | Duvaux, Odile | Blanchard, Dominique | Yu, Hai | Chen, Xi | Bach, Jean-Marie | Padler-Karavani, Vered | Viklicky, Ondrej | Soulillou, Jean-Paul | Xenothera [Nantes, France] | Department of Cell Research and Immunology ; Tel Aviv University (TAU) | Transplant laboratory [Prague, Czech Republic] ; Institute for Clinical and Experimental Medicine (IKEM) | Department of Nephrology [Prague, Czech Republic] (Transplant Center) ; Institute for Clinical and Experimental Medicine (IKEM) | Department of Chemistry [Univ California Davis] (Chemistry - UC Davis) ; University of California [Davis] (UC Davis) ; University of California (UC)-University of California (UC) | Immuno-Endocrinologie Cellulaire et Moléculaire (IECM) ; Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS) | Institut de transplantation urologie-néphrologie (ITUN) ; Université de Nantes (UN)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI) ; 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)-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) | Ministry of Health. | Czech Republic‐conceptual development of research organization (Institute for Clinical and Experimental Medicine‐IKEM, IN 0002300). | A grant from The Israeli Ministry of Science, Technology and Space No. 62466 and the 7th Framework Program FP7‐Health‐2013‐INNOVATION‐1‐603049 of the European Commission. | European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013)
International audience
Show more [+] Less [-]English. Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti-Neu5Gc antibodies at 6 and 12 months post-graft compared to the pre-existing levels due to the major early immunosuppression. However, in contrast, in a cross-sectional study there was a highly significant increase in anti-Neu5Gc IgGs levels at 6 months post-graft in the ATG-treated compared to non-treated patients(P = 0.007), with a clear hierarchy favouring anti-Neu5Gc over anti-Gal response. A sialoglycan microarray analysis revealed that the increased anti-Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc-containing glycans. Furthermore, some of the ATG-treated patients developed a shift in their anti-Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc-glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti-Neu5Gc repertoire shift. The clinical implications of these observations are discussed.
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