Are there advantages in the use of specific pathogen-free baboons in pig organ xenotransplantation models?

Xenotransplantation. 2014 May-Jun;21(3):287-90. doi: 10.1111/xen.12088. Epub 2014 Feb 18.

Abstract

Baboons have natural antibodies against pig antigens. We have investigated whether there are differences in anti-non-Gal pig antibody levels between baboons maintained under specific pathogen-free (SPF) conditions and those housed under conventional conditions (non-SPF) that might be associated with improved outcome after pig-to-baboon organ transplantation. Baboons (n = 40) were housed indoors (SPF n = 8) or in indoor/outdoor pens (non-SPF n = 32) in colonies of similar size and structure. Non-SPF colonies harbor a number of pathogens common to non-human primate species, whereas many of these pathogens have been eliminated from the SPF colony. Complete blood cell counts (CBC), blood chemistry, and anti-non-Gal IgM and IgG levels were monitored. There were no significant differences in CBC or blood chemistry between SPF and non-SPF baboons. Anti-non-Gal IgM levels were significantly lower in the SPF baboons than in the non-SPF baboons (MFI 7.1 vs. 8.8, P < 0.05). One SPF and two non-SPF baboons had an MFI >20; if these three baboons are omitted, the mean MFIs were 4.8 (SPF) vs. 7.5 (non-SPF) (P < 0.05). Anti-non-Gal IgG was minimal in both groups (MFI 1.0 vs. 1.0). As their levels of anti-non-Gal IgM are lower, baboons maintained under SPF conditions may be beneficial for xenotransplantation studies as the initial binding of anti-pig IgM to an α1,3-galactosyltransferase gene-knockout pig organ may be less, thus resulting in less complement and/or endothelial cell activation. However, even under identical SPF conditions, an occasional baboon will express a high level of anti-non-Gal IgM, the reason for which remains uncertain.

Keywords: anti-pig; antibody; baboon; pig; specific pathogen-free; xenotransplantation; α1,3-galactosyltransferase gene-knockout.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Heterophile / metabolism*
  • Biomarkers / metabolism
  • Female
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / metabolism
  • Male
  • Models, Animal*
  • Papio* / immunology
  • Papio* / metabolism
  • Papio* / surgery
  • Specific Pathogen-Free Organisms*
  • Swine* / immunology
  • Swine* / surgery
  • Transplantation, Heterologous*

Substances

  • Antibodies, Heterophile
  • Biomarkers
  • Immunoglobulin G
  • Immunoglobulin M