Since the landmark observation of Terasaki in 1969 that the presence of alloantibodies can be demonstrated by a simple test, i.e. the complement-dependent cytotoxicity cross-match before transplantation, hyperacute rejection has rarely been seen in renal transplantation and graft survival rates have greatly improved. Following a long period of intensive research in cellular mechanisms of allograft rejection, humoral immunity has now regained attention in the transplant community.
The demonstration by Feucht et al. that the presence of C4d staining - an indirect proof of the acitivity of humoral immune mechanisms within the graft - is associated with inferior graft outcome marked the renaissance of the interest into the effects of antibodies in renal transplantation. Indeed alloantibodies can be found in the serum of patients with C4d positive biopsies, and both features were shown to precede graft loss in many patients. Meanwhile, acute antibody mediated rejection has been accepted as separate entity in the Banff classification for allograft rejection and a variety of therapies targeting humoral effector mechanisms have been tested for its treatment. Strategies such as immunoadsorption, plasmapheresis, intravenous immunoglobulins (IVIG) or Rituximab (anti-CD20) as well as changes in standard immunosuppressive protocols have proven successful in the treatment of acute antibody mediated rejection. Studies to further define the role of alloantibodies for chronic allograft failure and strategies to treat their potential harmful effects on long term graft function are currently under investigation.