The Role of Anti-Neu5Gc IgM in Xenograft Antibody Mediated Rejection.

W. Hassanein,¹ G. Braileanu,¹ L. Burdorf,¹ W. Sun,¹ B. French,¹ C. Laird,¹ S. Sendil,¹ C. Ahn,³ D. Ayares,² R. Pierson III,¹ A. Azimzadeh.¹

¹University of Maryland School of Medcine, Baltimore, MD
²Revivicor, Blacksburg, VA
³Seoul National University Hospital, Seoul, Korea

Meeting: 2017 American Transplant Congress

Abstract number: B307

Keywords: FACS analysis, Lung transplantation, Xenoreactive antibodies, Xenotransplantation

Session Information

Session Name: Poster Session B: Xenotransplantation

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background:

Acute antibody mediated rejection due to preformed antibodies present in human serum remains a hurdle to successful xenotransplantation. Here, we measured anti-Neu5Gc-IgM antibody titers in human serum during ex-vivo perfusion of GalTKO.hCD46 and GalTKO.hCD46.Neu5GcKO genetically modified pig lungs.

Methods:

Pig aortic endothelial cells(PAECs)from GalTKO.hCD46 and GalTKO.hCD46. Neu5GcKO pigs were tested for Neu5Gc antigen expression using anti-Neu5Gc antibody. Human serum was collected at 0, 60 & 240 minutes of human blood perfusions of GalTKO.hCD46 (n=8) and GalTKO.hCD46.Neu5GcKO (n=5) pig lungs. Human embryonic kidney cells (HEK293) expressing porcine CMAH (HEK-pCMAH) and control (HEK) were incubated with either human plasma from lung perfusions or human serum pool. Anti-Neu5Gc IgM antibodies were measured by flow cytometry.

Results:

Standard human serum pool exhibited dose dependent IgM binding to HEK-pCMAH. GalTKO.hCD46 PAECs demonstrated the presence of Neu5Gc antigen, whereas Neu5GcKO PAECs lacked Neu5Gc antigen expression. Human serum anti-Neu5Gc IgM titer decreased [sim]40% during the ex vivo perfusion of GalTKO.hCD46 lungs, compared to Neu5GcKO lungs (p=0.0034). Conclusion:

Neu5Gc is absent antigenic target and contributor to antibody mediated rejection when Neu5GcKO porcine lung xenografts are perfused with human blood. Neu5GcKO is likely to improve preclinical, eventually clinical lung xenotransplantation.

[Figure1]Flow cytometry histogram of PAECs for Neu5Gc antigen expression in GalKO.CD46 pigs and Neu5GcKO pigs.

[Figure2]Percentage of anti-Neu5Gc IgM antibodies titer in human blood serum perfusing GalKO.CD46 and GalTKO.hCD46.Neu5GcKO porcine lungs.

CITATION INFORMATION: Hassanein W, Braileanu G, Burdorf L, Sun W, French B, Laird C, Sendil S, Ahn C, Ayares D, Pierson III R, Azimzadeh A. The Role of Anti-Neu5Gc IgM in Xenograft Antibody Mediated Rejection. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Hassanein W, Braileanu G, Burdorf L, Sun W, French B, Laird C, Sendil S, Ahn C, Ayares D, III RPierson, Azimzadeh A. The Role of Anti-Neu5Gc IgM in Xenograft Antibody Mediated Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/the-role-of-anti-neu5gc-igm-in-xenograft-antibody-mediated-rejection/. Accessed November 22, 2024.

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