Endothelial Cells in Antibody-Mediated Rejection of Kidney Transplantation: Pathogenesis Mechanisms and Therapeutic Implications

Table 2

The proposed mechanisms of endothelial cell-mediated accommodation in ABOi transplantation.

Study	Design	Key findings	Reference
Alleviation of apoptosis and complement
Bach et al.	Hamster to rat heart xenografts	Heart xenografts could acquire accommodation by upregulation of a number of antiapoptotic and anti-inflammatory genes including A20, Bcl-2, Bcl-xl, and hemeoxygenase-1 in endothelial cells.	[54]
Salama et al.	Human renal transplantation with HLA antibodies	Immunohistochemistry of the graft biopsies demonstrated increased expression of antiapoptotic protein Bcl-xl in glomerular and peritubular capillary endothelial cells. In vitro experiments confirmed that endothelial cells with upregulated Bcl-xl were rendered resistant to complement-dependent cytotoxicity.	[55]
Chen et al.	Renal transplantation in skin-presensitized nonhuman primates	Antiapoptotic proteins and complement regulatory proteins such as Bcl-2, CD59, CD46, and clusterin might contribute to allografts’ accommodation.	[56]
Iwasaki et al.	In vitro study of the effects of anti-HLA and anti-A/B antibody binding on complement-mediated cytotoxicity and signal transduction	Accommodation for anti-A/B antibodies relied on unregulated complement regulatory proteins CD55 and CD59 induced by suppressed ERK1/2 pathway, whereas in the background of anti-HLA antibodies activated PI3K/AKT pathway of endothelial cells led to expression of cytoprotective molecules such as hemeoxygenase-1 and ferritin H.	[57]
Blood group alteration or chimerism
Tanabe et al.	ABOi renal transplant recipients	Time-dependent downregulation of donor’s blood-type antigen on the graft endothelium was observed, which might contribute to the long-term accommodation after ABOi kidney transplantation.	[58]
Tanabe et al.	ABOi renal transplant recipients	Detectable antigenic chimerism on the graft endothelium was confirmed.	[59]