Porcine red blood cells express a polyagglutinable red blood cell phenotype: [Response]

We read with interest the letter by Swanson and Cooling, written in response to our recent article, in which they provide evidence that porcine red blood cells (pRBCs) express a polyagglutinable phenotype that is independent of α1,3-galactosyltransferase (αGal; linear B) expression. We fully agree with them that xenoantigenicity is still present in αGal gene-knockout pigs. As they provide evidence, other xenoantigens are present on pRBCs; one such example has been demonstrated by Zhu and Hurst to be N-glycolylneuraminic acid. Furthermore, knocking out the αGal gene may alter the glycosylation pattern on cell surfaces, as reported by Shinkel and coworkers, resulting in exposure of neoantigens, which could lead to destruction of these pig cells by antibodies or other constituents of the host immune response. One potential partial solution to this problem would be to replace the αGal epitopes with another oligosaccharide (through transgenic expression of a human gene) that would not be bound by human antibodies, for example, that for the H(O) blood group oligosaccharide.