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Published on: May 2, 2013
Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte
Apolline Salama1, Gwénaëlle Evanno, Noha Lim
11 Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France. 2 Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France. 3 Société d'Accélération du Transfert de Technologies Ouest Valorisation, Rennes, France. 4 Xenothera, Nantes, France. 5 Biomarker Discovery Research, Immune Tolerance Network, Bethesda, MD, USA. 6 IECM, Immuno-endocrinology, EA4644 Oniris, University of Nantes, USC1383 INRA, Oniris, Nantes, France. 7 Clinical Trials Group, Immune Tolerance Network, San Francisco, CA. 8 Division of Pediatric Endocrinology and Diabetes, University of California San Francisco, San Francisco, CA.
Rabbit antithymocyte globulin (ATG) treatment in type 1 diabetes patients triggers significant antibody responses against specific carbohydrate epitopes, potentially impacting treatment efficacy and safety.
Area of Science:
- Immunology
- Glycobiology
- Transplantation Immunology
Background:
- Antithymocyte globulin (ATG) is an immunosuppressive therapy for allograft rejection and autoimmune diseases.
- Rabbit ATG is immunogenic, causing serum sickness, as observed in type 1 diabetes patients during the START trial.
Purpose of the Study:
- To analyze anti-ATG specificities developed by patients in the START trial.
- To investigate the role of xenocarbohydrate epitopes in the immune response to rabbit ATG.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to analyze serial sera from the START study.
- Detection of antibodies against total ATG, galactose-α1-3-galactose (Gal), and Neu5Gc epitopes.
Main Results:
- Patients had pre-existing antibodies to ATG, Gal, and Neu5Gc at levels similar to healthy individuals.
- ATG treatment significantly increased IgM and IgG antibodies against these epitopes, peaking at 1 month and persisting for 1 year.
- A vigorous immune response against Gal and Neu5Gc epitopes was observed in patients treated with rabbit IgG without additional immunosuppression.
Conclusions:
- The anti-Gal and anti-Neu5Gc responses may create an inflammatory environment, potentially compromising ATG therapy efficacy.
- Developing ATG therapies using IgGs devoid of major xenoantigens could enhance safety and effectiveness.
