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

Ludmilla Le Berre, Richard Danger, Hoa L. Mai, Ron Amon, Shani Leviatan Ben-Arye, Sarah Bruneau, Thomas Senage, Helene Perreault, Milan Teraiya, Thi Van Ha Nguyen, Thierry Le Tourneau, Hai Yu, Xi Chen, Cesare Galli, Jean Christian Roussel, Rafael Manez, Cristina Costa, Sophie Brouard, Manuel Galinanes, Kristina M. HarrisStephen Gitelman, Emanuele Cozzi, Beatrice Charreau, Vered Padler-Karavani, Jean Paul Soulillou

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere12535
JournalXenotransplantation
DOIs
StatePublished - Jan 1 2019

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Transcriptome
Anti-Idiotypic Antibodies
Endothelial Cells
Genes
Cytokines
Chemokines
Serum
Diet
T-Lymphocytes
Heterologous Transplantation
Antibodies
Chemotaxis
Integrins
Endothelium
RNA
Apoptosis
Rabbits

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Le Berre, L., Danger, R., Mai, H. L., Amon, R., Leviatan Ben-Arye, S., Bruneau, S., ... Soulillou, J. P. (2019). Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome. Xenotransplantation, [e12535]. https://doi.org/10.1111/xen.12535

Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome. / Le Berre, Ludmilla; Danger, Richard; Mai, Hoa L.; Amon, Ron; Leviatan Ben-Arye, Shani; Bruneau, Sarah; Senage, Thomas; Perreault, Helene; Teraiya, Milan; Nguyen, Thi Van Ha; Le Tourneau, Thierry; Yu, Hai; Chen, Xi; Galli, Cesare; Roussel, Jean Christian; Manez, Rafael; Costa, Cristina; Brouard, Sophie; Galinanes, Manuel; Harris, Kristina M.; Gitelman, Stephen; Cozzi, Emanuele; Charreau, Beatrice; Padler-Karavani, Vered; Soulillou, Jean Paul.

In: Xenotransplantation, 01.01.2019.

Research output: Contribution to journalArticle

Le Berre, L, Danger, R, Mai, HL, Amon, R, Leviatan Ben-Arye, S, Bruneau, S, Senage, T, Perreault, H, Teraiya, M, Nguyen, TVH, Le Tourneau, T, Yu, H, Chen, X, Galli, C, Roussel, JC, Manez, R, Costa, C, Brouard, S, Galinanes, M, Harris, KM, Gitelman, S, Cozzi, E, Charreau, B, Padler-Karavani, V & Soulillou, JP 2019, 'Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome', Xenotransplantation. https://doi.org/10.1111/xen.12535
Le Berre, Ludmilla ; Danger, Richard ; Mai, Hoa L. ; Amon, Ron ; Leviatan Ben-Arye, Shani ; Bruneau, Sarah ; Senage, Thomas ; Perreault, Helene ; Teraiya, Milan ; Nguyen, Thi Van Ha ; Le Tourneau, Thierry ; Yu, Hai ; Chen, Xi ; Galli, Cesare ; Roussel, Jean Christian ; Manez, Rafael ; Costa, Cristina ; Brouard, Sophie ; Galinanes, Manuel ; Harris, Kristina M. ; Gitelman, Stephen ; Cozzi, Emanuele ; Charreau, Beatrice ; Padler-Karavani, Vered ; Soulillou, Jean Paul. / Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome. In: Xenotransplantation. 2019.
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abstract = "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.",
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AU - Le Berre, Ludmilla

AU - Danger, Richard

AU - Mai, Hoa L.

AU - Amon, Ron

AU - Leviatan Ben-Arye, Shani

AU - Bruneau, Sarah

AU - Senage, Thomas

AU - Perreault, Helene

AU - Teraiya, Milan

AU - Nguyen, Thi Van Ha

AU - Le Tourneau, Thierry

AU - Yu, Hai

AU - Chen, Xi

AU - Galli, Cesare

AU - Roussel, Jean Christian

AU - Manez, Rafael

AU - Costa, Cristina

AU - Brouard, Sophie

AU - Galinanes, Manuel

AU - Harris, Kristina M.

AU - Gitelman, Stephen

AU - Cozzi, Emanuele

AU - Charreau, Beatrice

AU - Padler-Karavani, Vered

AU - Soulillou, Jean Paul

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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