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...

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Bibliographic Details
Published in:American journal of transplantation 2003-08, Vol.3 (8), p.952-960
Main Authors: Park, Walter D., Grande, Joseph P., Ninova, Dora, Nath, Karl A., Platt, Jeffrey L., Gloor, James M., Stegall, Mark D.
Format: Article
Language:English
Subjects:
ABO Blood-Group System - immunology
Adaptation, Physiological - immunology
Autoantibodies - blood
Autoantibodies - genetics
Autoantibodies - immunology
bcl-2-Associated X Protein
bcl-X Protein
Blood group incompatibility
gene expression
Gene Expression Profiling
Glomerular Filtration Rate
Graft Survival
Humans
Immunohistochemistry
Kidney - metabolism
kidney transplantation
Kidney Transplantation - immunology
Mucin-1 - metabolism
Oligonucleotide Array Sequence Analysis
oligonucleotide microarray
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transplantation, Homologous - immunology
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Summary: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‐α 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.
ISSN:1600-6135
1600-6143
DOI:10.1034/j.1600-6143.2003.00179.x