Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
Grant support
Ministry of Health, Czech Republic-conceptual development of research organization
Health-2013-INNOVATION-1-603049
FP7 Health
62466
Israeli Ministry of Science, Technology and Space
PubMed
30620396
DOI
10.1111/eci.13069
Knihovny.cz E-resources
- MeSH
- Immunity, Cellular physiology MeSH
- Adult MeSH
- Transplantation, Homologous MeSH
- Immunoglobulin G pharmacology MeSH
- Immunologic Factors pharmacology MeSH
- Neuraminic Acids immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Antibodies immunology metabolism MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Thymocytes immunology MeSH
- Kidney Transplantation methods MeSH
- Transplantation Immunology physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Immunoglobulin G MeSH
- Immunologic Factors MeSH
- Neuraminic Acids MeSH
- N-glycolylneuraminic acid MeSH Browser
- Antibodies MeSH
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.
Department of Chemistry University of California Davis Davis California
Institut de Transplantation Urologie Néphrologie CHU Nantes Nantes France
References provided by Crossref.org
