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Transplantation. 2009 May 15;87(9):1308-17. doi: 10.1097/TP.0b013e3181a19afc.

Upregulation of CD59: potential mechanism of accommodation in a large animal model.

Author information

  • 1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.

Abstract

BACKGROUND:

Survival of ABO-mismatched kidneys with stable renal function despite the persistence of anti-ABO antibodies is called accommodation. The mechanism of accommodation is unclear, but may involve complement regulatory proteins such as CD59. The development of alpha-1,3-galactosyltransferase knock-out (GalT-KO) swine that produce anti-Gal antibodies provides a large animal model capable of determining the role of complement regulatory proteins in accommodation.

METHODS:

ELISA and antibody fluorescence-activated cell sorting were used to examine the rate of anti-Gal antibody expression as a function of age. Major histocompatibility complex-matched kidneys were transplanted from Gal-positive MGH miniature swine to MGH GalT-KO swine with systemic immunosuppression. One recipient underwent adsorbtion of anti-Gal antibodies before transplantation. Graft survival, antibody, and complement deposition patterns and CD59 expression were determined.

RESULTS:

Three animals rejected Gal-positive kidneys by humoral mechanisms. One animal with low titers of anti-Gal antibody displayed spontaneous accommodation and the animal that was treated with antibody adsorbtion also displayed accommodation. Rejected grafts had deposition of IgM, IgG, C3, and C5b-9 with low expression of CD59, whereas accommodated grafts had low deposition of C5b-9 and high expression of CD59. Retransplantation of one accommodated graft to a naïve GalT-KO animal confirmed that changes in the graft were responsible for the lack of C5b-9 deposition.

CONCLUSION:

GalT-KO miniature swine produce anti-Gal antibodies and titers increase with age. These anti-Gal antibodies can cause rejection of major histocompatibility complex-matched kidneys unless accommodation occurs. CD59 up-regulation seems to be involved in the mechanism of accommodation by preventing the formation of the membrane attack complex (MAC) on the accommodated graft.

PMID:
19424030
[PubMed - indexed for MEDLINE]
PMCID:
PMC2772119
Free PMC Article

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