Evidence against a pivotal role of preformed antibodies in delayed rejection of a guinea pig-to-rat heart xenograft.
BACKGROUND
Whereas the involvement of elicited xenoantibodies in delayed xenograft rejection is currently being substantiated, this study focuses on the role of the preformed fraction of xenoantibodies.


METHODS
To check the influence of the latter, we combined pretransplant complement inactivation (cobra venom factor) and antibody reduction (plasmapheresis) in a guinea pig-to-rat heart transplant model.


RESULTS
Antibody reduction on plasmapheresis before xenografting did not prolong delayed xenorejection in decomplemented rats, although the immunohistologic pattern lacked the immunoglobulin deposits along endothelial walls found in xenografts of merely decomplemented recipients. Astonishingly, plasmapheresis, if carried out 2 days before transplantation, almost tripled xenograft survival, although preformed antibody levels were completely restored and even rebounding at the time of grafting. The pattern and number of infiltrating cells did not differ in dependence of the timing of plasmapheresis nor did the proliferative response of lymphocytes in the mixed lymphocyte reaction differ. However, plasmapheresis led to a retarded decrease of the mononuclear cell tumor necrosis factor alpha secretory potential, which correlated well with a diminished immunohistologic staining of tumor necrosis factor alpha secreted by graft-infiltrating mononuclear cells.


CONCLUSIONS
These findings argue against a pivotal role of preformed xenoantibodies in the pathomechanistic process of delayed xenograft rejection and challenge the therapeutic strategy to reduce preformed xenoantibody levels before xenotransplantation in complement-inactivated recipients.
Grimm
H
H
Department of General and Thoracic Surgery and the Institute for Pathology, University of Giessen, Giessen, Germany. nut.grimm@chiru.med.uni-giessen.de
Mages
P
P
Lindemann
G
G
Potthoff
M
M
Bohnet
U
U
Korom
S
S
Ermert
L
L
D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology*; D010956:Plasmapheresis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous / Q000276:immunology*
D000906:Antibodies