Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: Implications for xenotransplantation in infants

Academic Article

Abstract

  • If an ABO-incompatible heart is transplanted into an infant before natural antibodies have developed to the specific donor carbohydrate A/B antigen(s), then B-cell tolerance to the donor A/B antigen is achieved, and these antibodies never develop. Anti-carbohydrate antibodies play a role in the rejection of wild type (WT) and α1,3-galactosyltransferase gene-knockout (GT-KO) pig xenografts. We investigated development of these antibodies in infant baboons and humans. Serum samples from infant baboons (n = 42) and humans (n = 42) were tested by flow cytometry for immunoglobulin M and immunoglobulin G binding to peripheral blood mononuclear cells from WT and GT-KO pigs, and for complement-dependent cytotoxicity. The presence of anti-blood group antibodies was tested in baboon serum. In infant baboons and humans, cytotoxic anti-Galα1,3Gal antibodies develop during the first 3 months, and steadily increase with age, whereas cytotoxic anti-nonGal antibodies are either absent or minimal in the majority of cases throughout the first year of life. Anti-blood group antibodies were not detected before 16 weeks of age. Our data suggest GT-KO pig organ/cell transplants could be carried out in early infancy in the absence of preformed cytotoxic anti-nonGalα1,3Gal antibodies. © 2007 The Authors.
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    Digital Object Identifier (doi)

    Author List

  • Rood PPM; Tai HC; Hara H; Long C; Ezzelarab M; Lin YJ; Van Der Windt DJ; Busch J; Ayares D; Ijzermans JNM
  • Start Page

  • 1050
  • End Page

  • 1058
  • Volume

  • 20
  • Issue

  • 12