Anti-Galalpha1-3Gal IgM/IgG antibody levels in infants: do they have a clinical relevance in pediatric xenotransplantation?

Anti-Galα1-3Gal IgM/IgG antibody levels in infants: do they have a clinical relevance in pediatric xenotransplantation?

BACKGROUND: Anti-Galalpha1-3Gal antibodies (anti-Gal) compose a major obstacle to xenotransplantation. As it is known, there is an immunological window during which infants are thought to have no xenoreactive antibodies. Therefore, we were interested in investigating the occurrence of these antibodies in newborns and infants up to 2 years of age. METHODS: IgM/IgG isotypes of anti-Gal from 74 serum samples of 16 mothers, with the respective cord bloods, and 42 infants of 4 age groups (Group I: day 1-6 months, II: 7-12 months, III: 13-18 months, and IV: 19-24 months) were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA). A synthetic Galalpha1-3Gal disaccharide-polyacrylamide glycoconjugate was used for coating and monoclonal antibodies were used for the detection of heavy chain isotypes. Antibody concentrations were referred to an internal standard and expressed as arbitrary ELISA units (U). Hemagglutination titers against rabbit erythrocytes (E(R)) were determined in addition. RESULTS: Maternal serum samples showed a wide interindividual variability (IgM: 87 +/- 33 U (mean +/- SD), IgG 59 +/- 39 U) whereas in cord blood no detectable IgM was seen in presence of IgG (52 +/- 34 U). From Group I to IV there was a gradual increase of anti-Gal IgM towards an average of 70% of the adult levels whereas IgG fell to an average of approximately 20% of cord blood levels. Hemagglutination titers followed an increasing tendency with cord blood starting from 1:16 and reaching 1:256 in Group IV. CONCLUSION: The humoral immune response to the Galalpha1-3Gal epitope (alpha-Gal) in infancy follows the generally known development of specific antibodies in humans.