Although there is little doubt that T cells are pivotal in the rejection of organ transplants, antibodies evoked against alloantigens in the graft can also mediate rejection. This process is called humoral rejection (antibody-mediated rejection), and it can take two forms. Hyperacute rejection occurs when preformed antidonor antibodies are present in the circulation of the recipient.
Such antibodies may be present in a recipient who has already rejected a kidney transplant. Multiparous women who develop anti-HLA antibodies against paternal antigens shed from the fetus may also have preformed antibodies to grafts taken from their husbands or children, or even from unrelated individuals who share HLA alleles with the husbands.
Prior blood transfusions can also lead to presensitization because platelets and white blood cells are rich in HLA antigens and donors and recipients are usually not HLA-identical. When preformed antidonor antibodies are present, rejection occurs immediately after transplantation because the circulating antibodies react with and deposit rapidly on the vascular endothelium of the grafted organ.
Complement fixation occurs, resulting in thrombosis of vessels in the graft, and ischemic death of the graft. With the current practice of cross-matching, that is, testing recipient’s serum for antibodies against donor’s cells, hyperacute rejection is no longer a significant clinical problem.
In recipients not previously sensitized to transplantation antigens, exposure to the class I and class II HLA antigens of the donor may evoke antibodies. The antibodies formed by the recipient may cause injury by several mechanisms, including complement-dependent cytotoxicity, inflammation, and antibody-dependent cell-mediated cytotoxicity.
The initial target of these antibodies in rejection appears to be the graft vasculature. Thus, antibody-dependent, or acute humoral rejection, is usually manifested by a vasculitis, sometimes referred to as rejection vasculitis.
See also
References
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