Immune response and histology of humoral rejection in kidney transplantation

Abstract

The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ.

Antibody-mediated rejection after lung transplantation

“…Complement split products bind to endothelial cells noncovalently and are subsequently inactivated by membrane cofactor protein, decay accelerating factor, and CD59 (51). However, unlike other complement split products, C4d binds the endothelium covalently via a thioester bond (51). This covalent bond is stable, resistant to shedding, and allows C4d to be detected long after other complement split products have been inactivated (51).…”

Very early acute rejection in an Australian and New Zealand kidney transplant population

“…Subsequent stages of the immune response to a transplanted graft as described below constitute adaptive or acquired immunity. As a highly sophisticated system with the unique capacity for polymorphism, specificity and memory, it is able to react to a broad selection of antigens which are then remembered so that repeat exposure will achieve a faster secondary response (31).…”

“…by CD4+ T cells cause B cells to secrete antibodies. Antibodies have two functions (24,31). One is complement-dependent and involves binding target cells and inducing their destruction by initiation of the classical complement system.…”

“…Significant ischaemic insults such as prolonged cold ischaemia time and donation after circulatory death may prevent C4d deposition (50,51). In chronic active ABMR, C4d deposition may occur sporadically so that staining is only intermittently positive (31).…”

“…Hyperacute rejection is a subset of ABMR that occurs within minutes to hours of organ implantation due to activation of the classical complement pathway by pre-existing recipient antibodies sensitive to donor tissue (31). These antibodies may be DSAs which form in response to previous sensitising events (blood transfusion, previous organ transplant or pregnancy), ABO blood group antibodies, or non-HLA antibodies.…”