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Transplant Accommodation in Highly Sensitized Patients: A Potential Role for Bcl‐xL and Alloantibody
Author(s) -
Salama Alan D.,
Delikouras Alex,
Pusey Charles D.,
Cook H. Terrance,
Bhangal Gurjeet,
Lechler Robert I.,
Dorling Anthony
Publication year - 2001
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2001.001003260.x
Subject(s) - allotransplantation , medicine , antibody , transplantation , immunology , umbilical vein , complement system , endothelium , peritubular capillaries , pathology , andrology , in vitro , biology , biochemistry
Transplantation of renal allografts into recipients with circulating anti‐HLA antibodies results in hyperacute rejection. In some cases, however, antibodies return without causing harm; this phenomenon has been termed ‘accommodation’. We have investigated this process in human allotransplantation. We removed anti‐HLA antibodies by immunoadsorption in seven highly sensitized dialysis patients who subsequently underwent renal transplantation. Immunohistochemistry of renal biopsies for IgG and anti‐apoptotic proteins was performed. We also developed a model of ‘accommodation’ using anti‐HLA antibodies eluted from sensitized patients and incubated with human umbilical vein endothelial cells (HUVECs) at different concentrations. Their effect on HUVEC phenotype was then analysed. Anti‐donor antibody returned in 4/7 patients, without evidence of hyperacute rejection. Three out of four of these ‘accommodated’ grafts showed specific endothelial up‐regulation of Bcl‐xL and 2/2 tested positive for endothelial IgG deposition. HUVECs incubated with subsaturating concentrations of anti‐HLA antibody showed increased expression of Bcl‐xL, were rendered refractory to endothelial cell activation and became resistant to complement‐mediated lysis. In contrast, HUVECs incubated with saturating concentrations underwent activation and expressed low levels of Bcl‐xL. In conclusion, endothelial Bcl‐xL expression defines the accommodation process in human allografts and this phenotype may be initiated by exposure of endothelium to low concentrations of anti‐donor HLA antibodies.