Characteristics of IgGs Produced in Neu5Gc and α1-3 Gal Double Knock-Out Pigs

A. Salama,^1,2 S. Conchon,¹ A. Perota,³ B. Martinet,¹ J.-P. Judor,¹ G. Evanno,¹ S. Le-Bas Bernardet,¹ L. Le Berre,¹ J. Hervouet,¹ D. Minault,¹ J.-P. Concordet,⁴ E. Dugast,¹ B. Vanhove,¹ J. Abadie,⁵ N. Gaide,⁵ I. Lagutina,³ R. Duchi,³ G. Lazzari,³ D. Sachs,⁶ O. Gauthier,⁷ S. Brouard,¹ E. Cozzi,⁸ G. Blancho,¹ H. Perreault,⁹ J.-M. Bach,¹⁰ C. Galli,^3,11 J.-P. Soulillou.¹

¹INSERM UMR 1064, ITUN, CHU de Nantes, Nantes University, Nantes, France
²Société
d'Accélération du Transfert de Technologies Ouest Valorisation, Rennes, France
³Avantea, Laboratory of Reproductive Technologies, Cremona, Italy
⁴INSERM U565, CNRS UMR7196, MNHN USM503, Paris, France
⁵AMaROC, ONIRIS, Nantes, France
⁶Massachusetts General Hospital, Transplantation Biology Research Center, Boston, MA
⁷Centre de Recherche et d'Investigation Préclinique, ONIRIS, Nantes, France
⁸Padua General Hospital and Consortium for Research in Organ Transplantation, Padua, Italy
⁹Chemistry Department, University of Manitoba, Winnipeg, Canada
¹⁰IECM, EA4644 University/ONIRIS USC1383 INRA, ONIRIS, Nantes, France
¹¹Dept. of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.

Meeting: 2015 American Transplant Congress

Abstract number: B289

Keywords: Antilymphocyte antibodies, Immunoglobulins (Ig), Pig, Xenotransplantation

Session Information

Session Name: Poster Session B: Vascularized Composite Tissue Allografts and Xenotransplantation

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Xenotransplantation offers a large number of potential applications, including solid organs, pancreatic islets, acellular tissues such as heart valves and skin grafts, and new bioreagents such as anti-thymocyte globulins (ATG). As an animal product, ATG may induce a humoral response against xeno-antigens and particularly, preexisting and elicited antibodies against α1-3 Gal and Neu5Gc might be deleterious for the function of this glycosylated molecule. We have obtained double KO pigs (DKOP) for CMAH and GT1, lacking Neu5Gc and α1-3 Gal and we present here some characteristics of their immune phenotype. DKOPs mount a significantly stronger response following immunization with the Jurkat human T-cell line than GT1 KO or wild-type pigs, likely due to their ligand-orphan SIGLEC status. Using ELISAs and mass spectrometry, we showed that Neu5Gc was present on IgGs from wild-type and GT1 KO lines whereas α1-3 Gal was not found in any of the pig lines tested. Finally, hyperimmune IgGs from DKOPs exhibit stronger complement-dependent cytotoxicity in vitro than IgGs from GT1 KO and wild-type counterparts, suggesting a better access of complement to DKO IgG Fc lacking Neu5Gc. In summary, our data show that besides being less immunogenic, IgGs from DKOPs are more abundantly produced and more cytotoxic than control IgGs.

To cite this abstract in AMA style:

Salama A, Conchon S, Perota A, Martinet B, Judor J-P, Evanno G, Bernardet SLe-Bas, Berre LLe, Hervouet J, Minault D, Concordet J-P, Dugast E, Vanhove B, Abadie J, Gaide N, Lagutina I, Duchi R, Lazzari G, Sachs D, Gauthier O, Brouard S, Cozzi E, Blancho G, Perreault H, Bach J-M, Galli C, Soulillou 11J-P. Characteristics of IgGs Produced in Neu5Gc and α1-3 Gal Double Knock-Out Pigs [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/characteristics-of-iggs-produced-in-neu5gc-and-1-3-gal-double-knock-out-pigs/. Accessed November 21, 2024.

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