Characterization of baboon anti-porcine IgG antibodies during acute vascular rejection of porcine kidney xenograft

• Published in: Xenotransplantation (Københaven) Vol. 9; no. 5; pp. 338 - 349
• Main Authors: Dehoux, Jean-Paul, De La Parra, Bernardo, Latinne, Dominique, Bazin, Hervé, Gianello, Pierre
• Format: Journal Article
• Language: English
• Published: Oxford UK Munksgaard International Publishers 01.09.2002
• Subjects: acute vascular rejection; Animals; anti-Gal antibodies; anti-μ monoclonal antibody; Antibodies, Anti-Idiotypic - pharmacology; Antibodies, Anti-Idiotypic - therapeutic use; Antibodies, Heterophile - biosynthesis; Antibodies, Heterophile - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibody Affinity; antibody characterization; Antibody Specificity; Aorta - cytology; baboon; Cells, Cultured - immunology; Cells, Cultured - transplantation; Disaccharides - immunology; E-Selectin - analysis; Endothelium, Vascular - chemistry; Endothelium, Vascular - immunology; Endothelium, Vascular - transplantation; Epitopes - immunology; Graft Rejection - immunology; Graft Rejection - therapy; Graft Survival; Immunization, Passive; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Immunoglobulin M - immunology; Kidney Transplantation - immunology; Papio - immunology; Swine - immunology; Transplantation, Heterologous - immunology; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1034/j.1399-3089.2002.01090.x

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.