Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy

Ron Amon, Shani Leviatan Ben-Arye, Limor Engler, Hai Yu, Noha Lim, Ludmilla Le Berre, Kristina M. Harris, Mario R. Ehlers, Stephen E. Gitelman, Xi Chen, Jean Paul Soulillou, Vered Padler-Karavani

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused increased global anti-Neu5Gc response. Here, for the first time we explore changes in anti- Neu5Gc IgG repertoire following the immunization elicited by ATG, compared with the basal antibodies repertoire that reflect exposure to dietary-Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to elucidate eventual differences in ATG-elicited repertoire, before/after ATG administration and track their kinetics (0, 1, 18 and 24 months). Response of all basal-pre-existing Neu5Gcspecific antibodies rapidly increased. This response peaked at one month post-ATG, with enhanced affinity, then resolved at 18-24 months. Induced-antibodies showed expanded diversity and de-novo recognition of different Neu5Gc-glycans, including endogenous glycolipids, that was further validated by affinity-purified anti-Neu5Gc antibodies from patients' sera. These findings strongly suggest that ATG-induced anti- Neu5Gc IgGs represent a secondary exposure to this dietary carbohydrate-antigen in humans, with immune memory. Given their modified recognition patterns, ATGevoked anti-Neu5Gc antibodies could potentially mediate biological effects different from pre-existing antibodies.

Original languageEnglish (US)
Pages (from-to)112236-112244
Number of pages9
JournalOncotarget
Volume8
Issue number68
DOIs
StatePublished - Jan 1 2017

Keywords

  • Anti-thymocyte globulin
  • Antibodies
  • Human
  • Immune response
  • Immunity
  • Immunology and Microbiology Section
  • N-glycolylneuraminic acid
  • Sialic acids

ASJC Scopus subject areas

  • Oncology

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    Amon, R., Ben-Arye, S. L., Engler, L., Yu, H., Lim, N., Le Berre, L., Harris, K. M., Ehlers, M. R., Gitelman, S. E., Chen, X., Soulillou, J. P., & Padler-Karavani, V. (2017). Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy. Oncotarget, 8(68), 112236-112244. https://doi.org/10.18632/oncotarget.23096