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

Juliette Rousse, Apolline Salama, Shani Leviatan Ben-Arye, Petra Hruba, Janka Slatinska, Gwénaëlle Evanno, Odile Duvaux, Dominique Blanchard, Hai Yu, Xi Chen, Jean Marie Bach, Vered Padler-Karavani, Ondrej Viklicky, Jean Paul Soulillou

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere13069
JournalEuropean Journal of Clinical Investigation
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Thymocytes
Grafts
Antibody Formation
Allografts
Polysaccharides
Anti-Idiotypic Antibodies
Immunoglobulin G
Carbohydrates
Rabbits
Galactose
Kidney
Antigens
Antibodies
Transplants
Mammals
Antilymphocyte Serum
T-cells
Microarrays
Epitopes
Microarray Analysis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

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

In: European Journal of Clinical Investigation, Vol. 49, No. 4, e13069, 01.04.2019.

Research output: Contribution to journalArticle

Rousse, J, Salama, A, Leviatan Ben-Arye, S, Hruba, P, Slatinska, J, Evanno, G, Duvaux, O, Blanchard, D, Yu, H, Chen, X, Bach, JM, Padler-Karavani, V, Viklicky, O & Soulillou, JP 2019, 'Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients', European Journal of Clinical Investigation, vol. 49, no. 4, e13069. https://doi.org/10.1111/eci.13069
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. / Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients. In: European Journal of Clinical Investigation. 2019 ; Vol. 49, No. 4.
@article{ca75e26406f94dc883b525634a248dce,
title = "Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients",
abstract = "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.",
author = "Juliette Rousse and Apolline Salama and {Leviatan Ben-Arye}, Shani and Petra Hruba and Janka Slatinska and Gw{\'e}na{\"e}lle Evanno and Odile Duvaux and Dominique Blanchard and Hai Yu and Xi Chen and Bach, {Jean Marie} and Vered Padler-Karavani and Ondrej Viklicky and Soulillou, {Jean Paul}",
year = "2019",
month = "4",
day = "1",
doi = "10.1111/eci.13069",
language = "English (US)",
volume = "49",
journal = "European Journal of Clinical Investigation",
issn = "0014-2972",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients

AU - Rousse, Juliette

AU - Salama, Apolline

AU - Leviatan Ben-Arye, Shani

AU - Hruba, Petra

AU - Slatinska, Janka

AU - Evanno, Gwénaëlle

AU - Duvaux, Odile

AU - Blanchard, Dominique

AU - Yu, Hai

AU - Chen, Xi

AU - Bach, Jean Marie

AU - Padler-Karavani, Vered

AU - Viklicky, Ondrej

AU - Soulillou, Jean Paul

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85062343695&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062343695&partnerID=8YFLogxK

U2 - 10.1111/eci.13069

DO - 10.1111/eci.13069

M3 - Article

C2 - 30620396

AN - SCOPUS:85062343695

VL - 49

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 4

M1 - e13069

ER -