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Transplantation. 2005 Feb 15;79(3 Suppl):S19-21.

Anti-HLA class I antibodies activate endothelial cells and promote chronic rejection.

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  • 1Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.


Transplant recipients exhibiting a humoral immune response to the allograft demonstrate lower graft survival and increased risk for the development of chronic rejection and transplant arteriosclerosis. Our studies suggest that anti-HLA class I antibodies (Ab) play an important role in controlling endothelial cell (EC) function by binding to class I molecules on the surface of the EC and transducing intracellular signals. Anti-HLA Ab exhibit two primary effector functions: stimulation of cell proliferation and up-regulation of cell survival genes. Importantly, the intracellular events initiated by class I ligation appear to be influenced by the concentration of the Ab. High-titered anti-HLA Ab stimulate cell proliferation whereas low-titered Ab activate the PI3K/Akt pathway and promote expression of cell survival proteins including Bcl-2 and Bcl-xL. Anti-HLA class I Ab may contribute to the process of chronic allograft rejection by promoting EC survival and proliferation.

[PubMed - indexed for MEDLINE]
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