Complement C4d in graft capillaries -- the missing link in the recognition of humoral alloreactivity

Staining of C4d in graft capillaries has emerged as a useful method to detect antibody-mediated rejections in situ. Demonstration of capillary C4d has provided substantial clinical results and allows several conclusions: Antidonor antibodies (preformed or produced de novo) activate complement directly in the graft. Capillary C4d is present in about 30% of biopsies with acute and chronic rejections and separates rejections with a humoral component from 'pure' cell-mediated rejections. Recognition of humoral alloreactivity is important, since effective treatment is now available. Since capillary C4d can appear and disappear at any time post transplantation, every transplant biopsy should be tested. Capillary C4d is now incorporated in the 'Banff classification'. The incidence of C4d-positive cases will probably decline because of the 'routine' application of potent immunosuppressants, including mycophenolate mofetil, that can inhibit antibody production. Presensitization, however, will remain a potential threat to allografts.