Treatment and prevention of chronic antibody-mediated rejection
Anthony Dorling
Kidney transplants do not last for the natural lifespan of most recipients, consigning
thousands of patients worldwide to return to dialysis each year, with significant
impact of morbidity and health costs. The commonest cause is chronic antibodymediated rejection (CAMR), but despite the name, relatively little is known about the
mechanisms leading to kidney transplants failure, and although there is strong
evidence associating antibodies with allograft failure, there is no evidence from
humans that anti-donor antibody is the causative agent.
In this talk I will summarise the results of our work exploring the activity of cellular
anti-donor immune responses in two cohorts of patients with biopsy-proven antibodymediated rejection, followed for ≥3 years. We have provided the first demonstration
in renal transplant recipients that B-lymphocytes process and present donor
alloantigens via the indirect pathway to interferon (
-producing T cells and
shown that the pattern of activity on ELISPOT closely correlates with graft outcome
over three years. This work forms the basis of two on-going clinical trials, both
targeting cellular immunity in patients with CAMR, which I will describe, in the context
of previous work looking at how to prevent or treat CAMR.
Our ambition is to significantly advance our understanding of the immune
mechanisms contributing to graft failure, and provide the foundations for rational,
safe and effective therapies to prolong grafts survival in patients with chronic
rejection.