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Xenotransplantation. 2019 Jul 10:e12535. doi: 10.1111/xen.12535. [Epub ahead of print]

Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome.

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Centre de Recherche en Transplantation et Immunologie (CRTI), INSERM, Université de Nantes, Nantes, France.
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Service de Chirurgie Cardio-Thoracique, CHU Nantes, Hopital Laennec, Nantes, France.
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
Institut du Thorax, INSERM UMR1087, CHU Nantes, Nantes, France.
Department of Chemistry, University of California-Davis, Davis, California.
Avantea, Laboratory of Reproductive Technologies and Fondazione Avantea, Cremona, Italy.
Intensive Care Medicine Department, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Infectious Diseases and Transplantation Division, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Department of Cardiac Surgery/Reparative Therapy of the Heart, Vall d'Hebron Research Institute and University Hospital Vall d'Hebron, Barcelona, Spain.
Immune Tolerance Network, Massachusetts General Hospital, Bathesda, Maryland.
Division of Pediatric Endocrinology and Diabetes, University of California at San Francisco, San Francisco, California.
Transplantation Immunology Unit, Padua University Hospital, Padova, Italy.


Humans cannot synthesize N-glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet-induced anti-Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet-induced anti-Neu5Gc Abs occurs in all normal individuals, endothelium activation by elicited anti-Neu5Gc Abs following a challenge with animal-derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity-purified anti-Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc-glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti-Neu5Gc Abs, compared with pre-existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti-Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre-existing or anti-human T-cell globulin (ATG)-elicited anti-Neu5Gc Abs. Compared with pre-existing anti-Neu5Gc Abs, which are normal component of ECs environment, elicited anti-Neu5Gc Abs down-regulated 66 genes, including master genes of EC function. Furthermore, elicited anti-Neu5Gc Abs combined with complement-containing serum down-regulated most transcripts mobilized by serum alone. Both types of anti-Neu5Gc Abs-induced a dose- and complement-dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre-existing anti-Neu5Gc Abs, ATG-elicited anti-Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro-inflammatory profile in vitro.


N-glycolylneuraminic acid (Neu5Gc); anti-Neu5Gc antibodies; endothelial cells; sialic acid; xenotransplantation


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