Anti-gal and anti-neu5gc responses in non-immunosuppressed patients following treatment with anti-thymocyte globulin - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Transplant International Année : 2017

Anti-gal and anti-neu5gc responses in non-immunosuppressed patients following treatment with anti-thymocyte globulin

Résumé

Background Polyclonal antihuman thymocyte rabbit IgGs (antithymocyte globulin [ATG]) are popular immunosuppressive drugs used to prevent or treat organ or bone-marrow allograft rejection, graft versus host disease, and autoimmune diseases. However, animal-derived glycoproteins are also strongly immunogenic and rabbit ATG induces serum sickness disease in almost all patients without additional immunosuppressive drugs, as seen in the Study of Thymoglobulin to arrest Type 1 Diabetes (START) trial of ATG therapy in new-onset type 1 diabetes. Methods Using enzyme-linked immunosorbent assay, we analyzed serial sera from the START study to decipher the various anti-ATG specificities developed by the patients in this study: antitotal ATG, but also antigalactose-α1-3-galactose (Gal) and anti-Neu5Gc antibodies, 2 xenocarbohydrate epitopes present on rabbit IgG glycans and lacking in humans. Results We show that diabetic patients have substantial levels of preexisting antibodies of the 3 specificities, before infusion, but of similar levels as healthy individuals. ATG treatment resulted in highly significant increases of both IgM (for anti-ATG and anti-Neu5Gc) and IgG (for anti-ATG, -Gal, and -Neu5Gc), peaking at 1 month and still detectable 1 year postinfusion. Conclusions Treatment with rabbit polyclonal IgGs in the absence of additional immunosuppression results in a vigorous response against Gal and Neu5Gc epitopes, contributing to an inflammatory environment that may compromise the efficacy of ATG therapy. The results also suggest using IgGs lacking these major xenoantigens may improve safety and efficacy of ATG treatment.
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Dates et versions

hal-02618751 , version 1 (25-05-2020)

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Paternité - Partage selon les Conditions Initiales

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  • HAL Id : hal-02618751 , version 1
  • PRODINRA : 415266
  • WOS : 000411688500048

Citer

Apolline Salama, Gwénaëlle Evanno, Noha Lim, Juliette Rousselot, Ludmilla Le Berre, et al.. Anti-gal and anti-neu5gc responses in non-immunosuppressed patients following treatment with anti-thymocyte globulin. Transplant International, 2017, 30, pp.21-21. ⟨hal-02618751⟩
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