C4d deposition and multilayering of peritubular capillary basement membrane in posttransplantation membranous nephropathy indicate its association with antibody-mediated injury

Membranous nephropathy (MN) may develop as recurrence or de novo after transplantation. Recently, autoimmune or alloimmune responses to unspecified glomerular antigens have been considered as a pathogenetic mechanism. To explore the relationship between antibody-mediated injury and posttransplantation MN, we tested C4d positivity using polyclonal antibody in renal allograft biopsy samples diagnosed as posttransplantation MN. A total of 19 cases (16 males and 3 females), including 2 recurrent and 7 de novo forms, were the subject of the study. On light microscopy, stage II was the most common (n = 9). In addition to glomerular capillary immunoglobulin (Ig)G deposits, all but 2 cases having only sclerotic glomeruli were C4d-positive in glomerular capillary walls. Twelve cases were also positive in cortical peritubular capillaries (PTCs): diffuse in 8 cases and focal in 4 cases. Two of 3 cases associated with acute rejection and 3 of 4 cases associated with chronic rejection were PTC C4d-positive. The frequency of C4d positivity in PTCs was significantly higher than that of posttransplantation IgA nephropathy (P =.028). In conclusion, a higher frequency of PTC C4d positivity suggests an involvement of chronic antibody-mediated injury in the evolution of posttransplantation MN.