Accommodation in ABO-incompatible kidney allografts, a novel mechanism of self-protection against antibody-mediated injury.
To elucidate the mechanism of self-protection against anti-donor blood-group antibody known as accommodation, we studied 16 human ABO-incompatible living-donor kidney transplant recipients at 3 and 12 months post transplantation. Both circulating anti-blood-group antibody and the target blood-group antigen in the graft were demonstrable in all patients after transplantation. Thirteen of 16 grafts had normal renal function and histology, while three grafts with prior humoral rejection demonstrated significant glomerulopathy and thus did not meet the criterion for accommodation. Using microarrays, we compared five 1-year protocol ABO-compatible renal graft biopsies to four accommodated ABO-incompatible graft biopsies. Significant alterations in gene expression in 440 probe sets, including SMADs, protein tyrosine kinases, TNF-alpha and Mucin 1 were identified. We verified these changes in gene expression using RT-PCR and immunohistochemistry. Heme oxygenase-1, Bcl-2 and Bcl-xl were not increased in ABO-incompatible grafts at any time-point. We conclude that accommodation is always present in well-functioning, long-surviving ABO-incompatible kidney transplants. This self-protection against antibody-mediated damage may involve several novel mechanisms including the disruption of normal signal transduction, attenuation of cellular adhesion and the prevention of apoptosis.
Park
Walter D
WD
Department of Surgery, Mayo Clinic, Rochester, MN, USA.
Grande
Joseph P
JP
Ninova
Dora
D
Nath
Karl A
KA
Platt
Jeffrey L
JL
Gloor
James M
JM
Stegall
Mark D
MD
D000017:ABO Blood-Group System / Q000276:immunology*; D000222:Adaptation, Physiological / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D018396:Mucin-1 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous / Q000276:immunology*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000017:ABO Blood-Group System; D001323:Autoantibodies; C494811:BCL2L1 protein, human; D018396:Mucin-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein