Characterization of baboon anti-porcine IgG antibodies during acute vascular rejection of porcine kidney xenograft.
In the pig-to-baboon model, the removal of anti-porcine natural antibodies abrogates hyperacute vascular rejection (HAVR), but the xenograft then undergoes an acute vascular rejection (AVR) concomitantly to the appearance of newly formed anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim of this work was to characterize the anti-porcine antibodies during AVR. Sera from anti-IgM-treated animals were assessed prior to the graft and at the time of AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine antibodies concentration as well as the IgG subtypes. The same sera were tested on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i) the cytolytic complement-dependent activity and (ii) the E-selectin expression. The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to discriminate the presence of Gal epitopes from the recognition of other porcine epitopes. We found that both anti-porcine IgM and IgG antibodies presented a significantly increased cytolytic activity and E-selectin expression on PAECs during AVR. These characteristics are related to an important increase of the antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl IgG1 subclass production, whereas the K affinity remained unchanged. The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies.
Laboratory of Experimental Surgery, Faculty of Medicine, Université Catholique de Louvain, ESP, Clos Chapelle aux Champs, Brussels, Belgium.
Jean-Paul
JP
Dehoux
Bernardo
B
de la Parra
Dominique
D
Latinne
Hervé
H
Bazin
Pierre
P
Gianello
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology / Q000627:therapeutic use; D000910:Antibodies, Heterophile / Q000096:biosynthesis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000915:Antibody Affinity; D000918:Antibody Specificity; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured / Q000276:immunology / Q000637:transplantation; D004187:Disaccharides / Q000276:immunology; D019040:E-Selectin / Q000032:analysis; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000628:therapy; D006085:Graft Survival; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D010215:Papio / Q000276:immunology*; D013552:Swine / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D004187:Disaccharides; D019040:E-Selectin; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C044203:anti-IgM; C055075:galactosyl-(1-3)galactose