IN-VIVO IMMUNOADSORPTION OF ANTIPIG ANTIBODIES IN BABOONS USING A SPECIFIC GAL-ALPHA-1-3GAL COLUMN

The major role of anti-alpha Gal antibodies in the hyperacute rejectio n of pig organs by humans and baboons has been clearly demonstrated, S pacered alpha-galactose disaccharide (Gal alpha 1-3Gal) hapten was pro duced by chemical synthesis and covalently attached to a flexible, hyd rophilic polymer (PAA), which in turn was covalently coupled to macrop orous glass beads, forming an immunoadsorbent that is mechanically and chemically stable and can be sterilized, The extracorporeal immunoads orption (EIA) of anti-alpha Gal antibodies using this column has been investigated in vivo in 3 baboons, In Baboon 1 (which had hyperacutely rejected a pig heart transplant 4 months previously, was not splenect omized, and did not receive any pharmacologic immunosuppression) the l evels of anti-alpha Gal antibody and antipig IgM and IgG, as well as s erum cytotoxicity, fell significantly after each of 3 EIAs but were no t eliminated, Serum cytotoxicity, antipig immunoglobulin and anti-alph a Gal antibody rose steeply within 24 hr of the final EIA, suggesting that the return of cytotoxicity was associated with anti-alpha Gal ant ibody, In Baboons 2 and 3 (which were immunologically naive and splene ctomized, and received triple drug immunosuppressive therapy) serum cy totoxicity was totally eliminated and anti-alpha Gal antibody and anti pig IgM and IgG levels were greatly reduced by courses of EIA. In Babo on 2, cytotoxicity and all antibody levels remained negligible for app roximately one week after the final (fourth) daily EIA, In Baboon 3, c ytotoxicity and antibody levels were maintained low by intermittent EI A (over a period of 13 days) for almost 3 weeks, although antipig IgM began to rebound 4 days after the final EIA, We conclude that, in an i mmunosuppressed, splenectomized baboon, repeated EIA using a specific alpha Gal disaccharide column will reduce antipig and anti-alpha Gal a ntibody levels and serum cytotoxicity significantly for several days, This reduction in cytotoxicity will almost certainly be sufficient to delay the hyperacute rejection of a transplanted pig organ, but furthe r studies are required to investigate whether it will be sufficient to allow accommodation to develop.