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

• Published in: Oncotarget Vol. 8; no. 68; pp. 112236 - 112244
• Main Authors: Amon, Ron, Ben-Arye, Shani Leviatan, Engler, Limor, Yu, Hai, Lim, Noha, Berre, Ludmilla Le, Harris, Kristina M., Ehlers, Mario R., Gitelman, Stephen E., Chen, Xi, Soulillou, Jean-Paul, Padler-Karavani, Vered
• Format: Journal Article
• Language: English
• Published: United States Impact journals 22.12.2017; Impact Journals LLC
• Subjects: Immunology; Life Sciences; Research Paper: Immunology; N-glycolylneuraminic acid; antibodies; Immunology; sialic acids; anti-thymocyte globulin; human
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.23096

Humans have circulating antibodies against diverse glycans containing -glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the 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 Neu5Gc-specific 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 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, ATG-evoked anti-Neu5Gc antibodies could potentially mediate biological effects different from pre-existing antibodies.