Plasma perfusion by apheresis through a Gal immunoaffinity column successfully depletes anti-Gal antibody: experience with 320 aphereses in baboons.
BACKGROUND
Anti-Galalpha1-3Gal (Gal) antibodies (Gal Ab) contribute to the rejection of porcine organs transplanted into primates. Extracorporeal immunoadsorption (EIA) has been developed to eliminate Gal Ab from the circulation.


METHODS
Between 1995 and 1999 we performed 320 EIAs in baboons using a COBE-Spectra apheresis unit incorporating a synthetic Gal immunoaffinity column. Three plasma volumes were immunoadsorbed on each occasion. The 221 consecutive EIAs performed in 41 immunosuppressed baboons between January 1997 and April 1999 form the basis of this review. Of these 41 baboons, 29 underwent a series of three or four EIAs at daily intervals, seven had multiple series of three EIAs, and the remainder underwent single or double EIAs. Serum 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 owing to technical difficulties and/or persistent hypotension. Mean pre-EIA Gal Ab levels in naive baboons were 33.1 microg/ml (IgM) and 14.5 microg/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 depletion remained at 80.1% (IgM) and 84.7% (IgG). The subsequent rate of return of Gal Ab depended on the immunomodulatory protocol used.


CONCLUSIONS
(1) With appropriate monitoring, EIA is an acceptably safe procedure, even in small (<10 kg) baboons. (2) Three consecutive EIAs are effective in removing >97% of Gal Ab. (3) In the majority of cases, return of Gal Ab begins within 24 h, irrespective of the immunomodulatory protocol.
Watts
A
A
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Foley
A
A
Awwad
M
M
Treter
S
S
Oravec
G
G
Buhler
L
L
Alwayn
I P
IP
Kozlowski
T
T
Lambrigts
D
D
Gojo
S
S
Basker
M
M
White-Scharf
M E
ME
Andrews
D
D
Sachs
D H
DH
Cooper
D K
DK
D000818:Animals; D002846:Chromatography, Affinity; D004187:Disaccharides / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005112:Extracorporeal Circulation; D006084:Graft Rejection / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood* / Q000302:isolation & purification; D007075:Immunoglobulin M / Q000097:blood* / Q000302:isolation & purification; D007163:Immunosorbent Techniques; D010215:Papio; D010477:Perfusion; D010956:Plasmapheresis / Q000379:methods*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
D004187:Disaccharides; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C055075:galactosyl-(1-3)galactose