title: Are there advantages in the use of specific pathogen-free baboons in pig organ xenotransplantation models?
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.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA; Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors.forename: Huidong
authors.initials: H
authors.lastname: Zhou
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.forename: Roman F
authors.initials: RF
authors.lastname: Wolf
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Gary
authors.initials: G
authors.lastname: White
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D010215:Papio / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D013047:Specific Pathogen-Free Organisms; D013552:Swine / Q000276:immunology / Q000601:surgery; D014183:Transplantation, Heterologous
chemical_list: D000910:Antibodies, Heterophile; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: anti-pig; antibody; baboon; pig; specific pathogen-free; xenotransplantation; α1,3-galactosyltransferase gene-knockout