Plasma perfusion by apheresis through a Gal immunoaffinity column successfully depletes anti-Gal antibody: experience with 320 aphereses in baboons

Background: Anti-Gal alpha 1-3Gal (Gal) antibodies (Gal Ab) contribute to t he rejection of porcine organs transplanted into primates. Extracorporeal i mmunoadsorption (EIA) has been developed to eliminate Gal Ab from the circu lation. Methods: Between 1995 and 1999 we performed 320 EIAs in baboons using a COB E-Spectra apheresis unit incorporating a synthetic Gal immunoaffinity colum n. Three plasma volumes were immunoadsorbed on each occasion. The 221 conse cutive EIAs performed in 41 immunosuppressed baboons between January 1997 a nd April 1999 form the basis of this review. Of these 41 baboons, 29 underw ent a series of three or four EIAs at daily intervals, seven had multiple s eries of three EIAs, and the remainder underwent single or double EIAs. Ser um Gal Ab levels were monitored by ELISA before and at intervals after the course of EIA. Results: There were two fatal complications, one from a respiratory mishap (unrelated to the EIA) and one from persistent hypotension unresponsive to therapeutic interventions. Seven procedures (3%) were terminated early owin g to technical difficulties and/or persistent hypotension. Mean pre-EIA Gal Ab levels in naive baboons were 33.1 mu g/ml (IgM) and 14.5 mu g/ml (IgG). Immediately after three consecutive EIAs, IgM was depleted by a mean of 97 .3% and IgG by 99.4%. By 18 to 24 h later, Gal Ab was returning but depleti on remained at 80.1% (IgM) and 84.7% (IgG). The subsequent rate of return o f Gal Ab depended on the immunomodulatory protocol used. Conclusions: (1) With appropriate monitoring, EIA is an acceptably safe pro cedure, even in small(<10 kg) baboons. (2) Three consecutive EIAs are effec tive in removing >97% of Gal Ab. (3) In the majority of cases, return of Ga l Ab begins within 24 h, irrespective of the immunomodulatory protocol.