Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts

Elizabeth A. Davis, Scott K. Pruitt, Peter Schuyler Greene, Sherif Ibrahim, Tuan T. Lam, James L. Levin, William M. Baldwin, Fred Sanfilippo

Research output: Contribution to journalArticle

Abstract

Complement (C) inhibition alone using a recombinant soluble form of complement receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent irreversible accelerated acute rejection of discordant pig-to- cynomolgus monkey cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute rejection, which is associated with a rise in serum xenoreactive antibody (Ab) and a cellular infiltrate, triple therapy with standard immunosuppressive agents (cyclosporine, cyclophosphamide, and steroids [CCS]) was combined with continuous C inhibition using sCR1. Each of two monkeys that received sCR1 + CCS showed minimal evidence of rejection when killed on days 21 and 32 in comparison to a monkey that received sCRI + subtherapeutic CCS (rejected at 11 days) and a control that received CCS alone (rejected at 38 min). Prolonged xenograft survival was associated with low Ab levels and a minimal cellular infiltrate, suggesting that combined inhibition of C, xenoreactive Ab responses, and cellular immunity may be a useful approach in overcoming the immune barriers to discordant xenotransplantation.

Original languageEnglish (US)
Pages (from-to)1018-1023
Number of pages6
JournalTransplantation
Volume62
Issue number7
DOIs
StatePublished - Oct 15 1996

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Heterografts
Cyclophosphamide
Primates
Cyclosporine
Antibody Formation
Swine
Steroids
Haplorhini
Complement Receptors
Heterologous Transplantation
Macaca fascicularis
Antibodies
Immunosuppressive Agents
Cellular Immunity
Serum
Therapeutics

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts. / Davis, Elizabeth A.; Pruitt, Scott K.; Greene, Peter Schuyler; Ibrahim, Sherif; Lam, Tuan T.; Levin, James L.; Baldwin, William M.; Sanfilippo, Fred.

In: Transplantation, Vol. 62, No. 7, 15.10.1996, p. 1018-1023.

Research output: Contribution to journalArticle

Davis, Elizabeth A. ; Pruitt, Scott K. ; Greene, Peter Schuyler ; Ibrahim, Sherif ; Lam, Tuan T. ; Levin, James L. ; Baldwin, William M. ; Sanfilippo, Fred. / Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts. In: Transplantation. 1996 ; Vol. 62, No. 7. pp. 1018-1023.
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