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Detection of alloantibody deposition in allografts: capillary C4d deposition as a marker of humoral rejection

2004; Lippincott Williams & Wilkins; Volume: 9; Issue: 1 Linguagem: Inglês

10.1097/00075200-200403000-00007

1531-7013

Solange Moll, Manuel Pascual,

Transplantation: Methods and Outcomes

Purpose of review Studies in recent years have demonstrated that peritubular capillary C4d deposition is diagnostic of humoral rejection in kidney allografts. In organ transplantation, the fragment C4d is generated during antibody-mediated activation of the classical pathway of complement. Notably, a strong association has been shown between capillary C4d deposits in renal allograft biopsies and donor-specific anti-HLA class I and/or class II alloantibodies in recipient sera. Moreover, C4d appears to be a valuable prognostic marker of graft survival. These observations have led to an update in the histopathological Banff `97 classification of renal allograft rejection and the integration of the C4d immunostaining in its diagnostic criteria, so that allograft rejection is now subdivided into “antibody-mediated rejection” (humoral rejection) and “acute/active cellular rejection”. Importantly, new therapeutic strategies to remove antidonor alloantibodies from the recipient's serum to improve the prognosis of acute humoral rejection have been developed. Recent findings Recent data suggest that chronic renal allograft rejection might also be monitored by the detection of C4d in biopsies. Capillary C4d deposition correlates with the typical histopathologic lesions of chronic rejection, and it can precede the development of these lesions. Moreover, similarly to acute humoral rejection, a correlation has been shown between biopsy C4d deposits and antidonor alloantibodies in the patient's serum. Therefore, the presence of capillary C4d reflects an active humoral immune reaction (ie, it identifies features of true alloimmune injury). The efficacy of newer immunosupressants in suppressing antidonor humoral antibody production in patients with chronic allograft dysfunction remains to be determined prospectively in controlled clinical trials. Summary In this review, we discuss the current clinical and pathological knowledge of alloantibody-mediated rejection in organ transplants, particularly in kidney allografts. Recent studies analyzing the contribution of capillary C4d staining in diagnosis of humoral rejection in recipients of nonrenal allografts are also discussed.