DEPLETION OF ANTI-GAL-ALPHA-1-3GAL ANTIBODY IN BABOONS BY SPECIFIC ALPHA-GAL IMMUNOAFFINITY COLUMNS

Ongoing studies at our center on facilitating transplantation of disco rdant xenogeneic organs are focused on tolerance induction. To abrogat e hyperacute rejection, we have used adsorption methods to eliminate n atural anti-Gal alpha 1-3Gal (alpha Gal) antibodies from the circulati on of baboons. We have analyzed data concerning antibody removal in ba boons that were 1) immunologically naive, 2) receiving conventional ph armacologic immunosuppressive therapy (IS), and 3) treated with a cond itioning regimen for tolerance induction. We compared the efficiency o f removing alpha Gal antibody 1) by perfusion of whole blood through a n alpha Gal affinity column (CP; n=5) with 2) perfusion of plasma (sep arated from cellular components by apheresis) through an alpha Gal col umn (CPA; n=39). Our studies demonstrate that 1) CP and CPA are equall y effective in removing anti-alpha Gal antibody, 2) CPA is the method of choice if multiple adsorptions are required, 3) CPA in naive animal s transiently affects levels of total IgG and ISM, 4) four CPAs repeat ed at 2-4 day intervals in association with heavy IS reduce the pool o f anti-alpha Gal antibody and total Ig, and 5) splenectomy and/or IS d elay the return of anti-alpha Gal antibody.