Rejection of the Renal Allograft in the Absence of Demonstrable Antibody and Complement

Recent literature has stressed the prominent role of antibodies in graft loss. This study was designed to assess a growing perception that T cell-mediated rejection (TCMR) is no longer clinically relevant. Five hundred forty-five renal allograft recipients over a 3-year period were screened for biopsies with: (a) TCMR including borderline change (BL), (b) negative complement protein C4 degradation fragment, and (c) absence of donor-specific antibody at time of transplant, within 30 days of the biopsy, and up to 4 measurements at later time points. These stringent requirements identified 28 “pure” cases of late TCMR/BL. Low-grade glomerulitis, peritubular capillaritis, or chronic transplant glomerulopathy were found in 9/28 (32%) biopsies. Serum creatinine showed complete short-term remission in 7/10 (70%) BL and 9/18 (50%) TCMR patients 1 month postbiopsy. Yet, both treated and untreated patients demonstrated further decline in graft function as assessed by serum creatinine and estimated glomerular filtration rate. Late TCMR seen in 7.9% of biopsies can contribute to significant deterioration of graft function in patients in whom the dominant contribution of antibody-mediated injury has been reasonably excluded. Our data also reinforce existing literature showing that microvascular lesions do not have absolute specificity for a diagnosis of antibody-mediated rejection.