Abstract
Evidence from several transplant centers indicates that a substantial proportion of acute and chronic renal allograft rejection is caused by antibodies to donor antigens. Antibody-mediated injury arises despite potent anti-T cell pharmacological agents, and probably requires different therapy. Acute humoral rejection occurs in 20-30% of acute rejection cases, has a poorer prognosis than cellular rejection, and is refractory to conventional immunosuppressive therapy. C4d deposition in peritubular capillaries of renal allografts has been demonstrated to be a sensitive and diagnostic in-situ marker of acute humoral rejection that correlates strongly with the presence of circulating donor-specific antibodies. Biopsies with chronic allograft arteriopathy or glomerulopathy also have a high frequency of C4d deposition and donor-specific antibodies. The vessels of other organs, notably the heart, can also be targets of humoral rejection. New polyclonal C4d antibodies work in paraffin sections. Pitfalls in C4d staining have been identified and must be considered in the valid interpretation of results. As the histology is variable, the current diagnosis of humoral rejection in biopsies relies on the demonstration of C4d, a component of the classical complement pathway, in peritubular capillaries. The new classification of renal allograft rejection incorporates humoral and cellular mechanisms of injury, with the diagnostic criteria of each. This should prove useful in guiding clinical treatment, and stratifying drug trials, replacing obsolete terms such as 'vascular rejection'. Specific therapeutic strategies for humoral rejection with controlled trials targeting the humoral limb of immunosuppression are needed.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.