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Eur J Clin Invest. 2019 Apr;49(4):e13069. doi: 10.1111/eci.13069. Epub 2019 Feb 25.

Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients.

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Xenothera, Nantes, France.
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Chemistry, University of California-Davis, Davis, California.
Immuno-Endocrinology Unit, EA4644 University/ONIRIS USC1383 INRA, Pathophysiology Department, ONIRIS-Nantes-Atlantic College of Veterinary Medicine and Food Sciences, Nantes, France.
Centre de Recherche en Transplantation et Immunologie, UMR 1064, INSERM, Université de Nantes, Nantes, France.
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.


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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