INTRAVENOUS IMMUNOGLOBULINS FOR THERAPEUTIC USE CONTAIN ANTIIDIOTYPESAGAINST XENOPHILE ANTIBODIES AND PROLONG DISCORDANT GRAFT-SURVIVAL

Xenotransplantation between discordant species leads to a graft surviv al of a few minutes, due to binding of natural antibodies to the xenog eneic endothelial cells, complement activation, and endothelial cell a ctivation. Polyclonal human immunoglobulins for intravenous use (IVIg) from normal donors have been proven effective in a variety of antibod y-mediated disorders and contain anti-idiotypic antibodies directed ag ainst a number of disease-associated and natural antibodies. We have s hown that administration of IVIg delays rejection of a guinea pig hear t to a rat. We demonstrate herein that IVIg can inhibit the binding of xenoreactive rat IgG antibodies to guinea pig endothelial cells. This inhibition is likely due to the presence, among IVIg, of anti-idiotyp ic antibodies as F(ab')(2) fragments of IVIg were as effective as whol e IVIg. In addition, natural anti-endothelium rat antibodies were reta ined on a column of F(ab')(2) fragments of IVIg coupled to Sepharose. The degree of inhibition of binding of IgG natural antibodies correlat ed with the survival of the xenograft when IVIg was administered prior to transplantation. Thus IVIg prolong xenograft survival through idio typic-anti-idiotypic interactions with natural xenoreactive antibodies of the IgG isotype. (C) 1998 Academic Press.