Pathologic features of acute renal allograft rejection associated with donor-specific antibody, Analysis using the Banff grading schema

Abstract

Alloantibody frequently appears during the immune response to alloantigens in renal transplant recipients. We studied whether the presence of antibody against donor class I antigens correlated with the clinical and pathologic features of acute rejection episodes. We identified patients who had (1) clinical evidence of acute rejection, (2) a renal biopsy showing pathologic features of acute rejection, defined by the Banff criteria, and (3) pre- and posttransplant sera screened against donor T cells. We divided these patients into those with or without donor-specific alloantibody reactive with donor T cells. Of 44 patients with biopsy-proven rejection, 20 were antibody negative (Ab-R) and 24 were antibody positive (Ab+R). The biopsies from Ab+R patients had a higher incidence of severe vasculitis (P=0.0009) and glomerulitis (P=0.01). Fibrin thrombi in the glomeruli and/or vessels, fibrinoid necrosis, and dilatation of peritubular capillaries were also more frequent in the Ab+R group. Infarction was present in biopsy specimens from 9/24 Ab+R patients versus none in the Ab-R group (P=0.002). The Ab+R biopsy specimens more often had polymorphonuclear leukocytes in the peritubular capillaries (P=0.003). In contrast, specimens of Ab-R patients showed tubulitis more often than the specimens of Ab+R patients: moderate and severe tubulitis was present in 19/20 (95%) Ab-R patients versus 12/24 (50%) Ab+R patients (P=0.002). Graft loss was increased in Ab+R patients, particularly in the first 3 months (12/24 compared with 3/20, P=0.025). Thus, during biopsy-proven acute rejection episodes, anti-class I antibody correlates with severe vascular lesions, glomerulitis, and infarction, whereas more severe tubulitis predominates in rejection episodes without antibody.