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Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.

Publication ,  Journal Article
Martens, GR; Reyes, LM; Li, P; Butler, JR; Ladowski, JM; Estrada, JL; Sidner, RA; Eckhoff, DE; Tector, M; Tector, AJ
Published in: Transplantation
April 2017

Antipig antibodies are a barrier to clinical xenotransplantation. We evaluated antibody binding of waitlisted renal transplant patients to 3 glycan knockout (KO) pig cells and class I swine leukocyte antigens (SLA).Peripheral blood mononuclear cells from SLA identical wild type (WT), α1, 3-galactosyltransferase (GGTA1) KO, GGTA1/ cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) KO, and GGTA1/ CMAH /b1,4 N-acetylgalactosaminyl transferase (B4GalNT2) KO pigs were screened for human antibody binding using flow cytometric crossmatch (FCXM). Sera from 820 patients were screened on GGTA1/CMAH/B4GalNT2 KO cells and a subset with elevated binding was evaluated further. FCXM was performed on SLA intact cells and GGTA1/SLA class I KO cells after depletion with WT pig RBCs to remove cell surface reactive antibodies, but leave SLA antibodies. Lastly, human and pig reactive antibodies were eluted and tested for cross-species binding and reactivity to single-antigen HLA beads.Sequential glycan KO modifications significantly reduce antibody binding of waitlisted patients. Sera exhibiting elevated binding without reduction after depletion with WT RBCs demonstrate reduced binding to SLA class I KO cells. Human IgG, eluted from human and pig peripheral blood mononuclear cells, interacted across species and bound single-antigen HLA beads in common epitope-restricted patterns.Many waitlisted patients have minimal xenoreactive antibody binding to the triple KO pig, but some HLA antibodies in sensitized patients cross-react with class I SLA. SLA class I is a target for genome editing in xenotransplantation.

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Published In

Transplantation

DOI

EISSN

1534-6080

ISSN

0041-1337

Publication Date

April 2017

Volume

101

Issue

4

Start / End Page

e86 / e92

Related Subject Headings

  • Waiting Lists
  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Protein Binding
  • Phenotype
  • N-Acetylgalactosaminyltransferases
  • Mixed Function Oxygenases
  • Kidney Transplantation
  • Immunoglobulin G
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Martens, G. R., Reyes, L. M., Li, P., Butler, J. R., Ladowski, J. M., Estrada, J. L., … Tector, A. J. (2017). Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs. Transplantation, 101(4), e86–e92. https://doi.org/10.1097/tp.0000000000001646
Martens, Gregory R., Luz M. Reyes, Ping Li, James R. Butler, Joseph M. Ladowski, Jose L. Estrada, Richard A. Sidner, Devin E. Eckhoff, Matt Tector, and A Joseph Tector. “Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.Transplantation 101, no. 4 (April 2017): e86–92. https://doi.org/10.1097/tp.0000000000001646.
Martens GR, Reyes LM, Li P, Butler JR, Ladowski JM, Estrada JL, et al. Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs. Transplantation. 2017 Apr;101(4):e86–92.
Martens, Gregory R., et al. “Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.Transplantation, vol. 101, no. 4, Apr. 2017, pp. e86–92. Epmc, doi:10.1097/tp.0000000000001646.
Martens GR, Reyes LM, Li P, Butler JR, Ladowski JM, Estrada JL, Sidner RA, Eckhoff DE, Tector M, Tector AJ. Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs. Transplantation. 2017 Apr;101(4):e86–e92.

Published In

Transplantation

DOI

EISSN

1534-6080

ISSN

0041-1337

Publication Date

April 2017

Volume

101

Issue

4

Start / End Page

e86 / e92

Related Subject Headings

  • Waiting Lists
  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Protein Binding
  • Phenotype
  • N-Acetylgalactosaminyltransferases
  • Mixed Function Oxygenases
  • Kidney Transplantation
  • Immunoglobulin G