Untitled - Roche Trasplantes

PROTOCOL BIOPSIES
AND THE DIAGNOSIS
OF HUMORAL REJECTION
M. Mengel
INTRODUCTION
The humoral theory of allograft rejection proposes that an organ transplant is rejected
by the action of antibodies, not cells. However, for the last three decades, T cells have
been in the main focus of transplant research. T cells are regarded to be the pivotal effector
and regulatory cells in allograft rejection. This conception was based on early findings
in animal models and humans that T cell depletion prevents allograft rejection.
Considerable therapeutic success was achieved by modern drugs suppressing T cells
and improving short-term allograft survival to >90% in the first year after transplantation.
Already in 1990, Halloran et al. drew attention to anti-donor antibodies as a further cause
of severe allograft dysfunction. Still today a considerable percentage of renal allografts
undergo episodes of acute rejection, frequently leading to chronic rejection and subsequent
graft lost. However, against the background of modern, very effective anti-T cell
immunosuppression an continuously increasing number of recent publications reflect a
crucial role of antibodies (humorale rejection) besides T cells (cellular rejection) in renal
allograft rejection.
This overview focuses on the morphological findings in acute and chronic humoral (antibody-mediated)
rejection in renal allograft biopsies. The mechanisms of antibody-mediated
allograft injury and graft resistance to immunological injury (i.e., accommodation)
will be described to stimulate the discussion of new therapeutical strategies in case of
humoral rejection.
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