SERUM CYTOTOXICITY TO PIG CELLS AND ANTI-??GAL ANTIBODY LEVEL AND SPECIFICITY IN HUMANS AND BABOONS

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Abstract
Background. Removal and/or "neutralization" of anti-Galα1-3Gal (αGal) antibodies can prevent or delay the hyperacute rejection of pig organs transplanted into primates. Aim. To determine variations in (1) cytotoxicity to pig kidney (PK15) cells, (2) anti-αGal antibody level, and (3) specificity in adult human (n=46) and baboon (n=38) sera. Methods. Cytotoxicity to PK15 cells was determined by adding rabbit complement to heat-inactivated serum, using a two-color fluorescent dye to distinguish live and dead cells. Anti-αGal antibody level was determined by ELISA using αGal trisaccharide type 2-BSA glycoconjugate as antigen target. Specificity determined by ELISA using four different αGal-BSA glycoconjugates: (disaccharide, trisaccharides type 2 and 6, and pentasaccharide). Results. Cytotoxicity of human AB sera varied from 30-100% PK15 relative cell damage (%RCD), although that of baboon sera of all blood groups varied from 35-100% RCD. In human AB sera, anti-αGal antibody level (at a dilution of 1:80) varied from undetectable to 0.75 (OD at 405 nm), although in baboon sera of all blood groups, anti-αGal antibody level varied from undetectable to >2.0. There was no correlation between anti-αGal antibody level and serum cytotoxicity in either species. Specificity varied among individuals in both human and baboon sera. Conclusions. These studies have demonstrated (1) considerable variation in cytotoxicity and anti-αGal antibody level in human and baboon sera, but a lack of correlation between these two parameters; (2) considerable variation in the specificity of anti-αGal antibodies; (3) blood group B human and baboon sera have lower levels of anti-αGal antibodies; (4) no relation between blood group and specificity of anti-αGal antibodies. Although there are minor differences in the parameters measured, baboons would appear to be suitable surrogates for humans in the pig-to-primate xenograft model.

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