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

Journal Article

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 sCR1 + 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.

Full Text

Duke Authors

Cited Authors

  • Davis, EA; Pruitt, SK; Greene, PS; Ibrahim, S; Lam, TT; Levin, JL; Baldwin, WM; Sanfilippo, F

Published Date

  • October 15, 1996

Published In

Volume / Issue

  • 62 / 7

Start / End Page

  • 1018 - 1023

PubMed ID

  • 8878398

International Standard Serial Number (ISSN)

  • 0041-1337

Language

  • eng

Conference Location

  • United States