TY - JOUR
T1 - Accommodation in ABO-incompatible kidney allografts, a novel mechanism of self-protection against antibody-mediated injury
AU - Park, Walter D.
AU - Grande, Joseph P.
AU - Ninova, Dora
AU - Nath, Karl A.
AU - Platt, Jeffrey L.
AU - Gloor, James M.
AU - Stegall, Mark D.
PY - 2003/8
Y1 - 2003/8
N2 - 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.
AB - 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.
KW - Blood group incompatibility
KW - Gene expression
KW - Immunohistochemistry
KW - Kidney transplantation
KW - Oligonucleotide microarray
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U2 - 10.1034/j.1600-6143.2003.00179.x
DO - 10.1034/j.1600-6143.2003.00179.x
M3 - Article
C2 - 12859529
AN - SCOPUS:0042766395
SN - 1600-6135
VL - 3
SP - 952
EP - 960
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 8
ER -