A. Bartholomew et al., UTILITY OF XENOGRAFTS - LACK OF CORRELATION BETWEEN PRA AND NATURAL ANTIBODIES TO SWINE, Xenotransplantation, 4(1), 1997, pp. 34-39
Among the patients that might potentially benefit from the availabilit
y of xenografts are those in kidney failure who demonstrate high level
s of antibody reactivity to panels of typing lymphocytes. Such individ
uals with high PRA (panel reactive antibody) are unlikely to receive a
renal allograft because they are highly sensitized to the vast majori
ty of potential donors. In addition, all humans have demonstrable leve
ls of natural antibodies reactive to distantly related species such as
the pig. If there were a correlation between PRA and levels of natura
l antibodies, then such patients would also be at greater risk for hyp
eracute rejection of xenografts. We have therefore examined, in a blin
ded fashion, the porcine lymphocyte reactivity of sera from PRA positi
ve donors. Subsets of the 105 sera tested were grouped by PRA level an
d analyzed for levels of natural antibodies detectable by a complement
-dependent cytotoxicity assay on porcine lymphocytes. There was no sig
nificant difference in the range of titers of natural antibodies betwe
en subsets. Thus, there was no demonstrable correlation between levels
of PRA and levels of natural antibodies to porcine lymphocytes. In ad
dition, we studied the sera of 11 highly sensitized patients who recei
ved renal allografts and conventional triple drug immunosuppression in
order to determine whether immunosuppression to maintain a vasculariz
ed allograft had an effect on PRA and/or xenoreactivity. Mean post-ope
rative PRA was significantly lower than mean pre-operative PRA, while
there was no significant difference in xenoreactivity. Thus, pretransp
lant immunosuppression may permit an increased opportunity to identify
compatible human donors for highly sensitized recipients and will not
help or hinder the pre-transplant conditioning of a candidate for xen
otransplantation.