Significance of C4d deposition in antibody-mediated rejection

The C4d staining as a special tissue marker for humoral immunity has served criteria of pathological diagnosis for antibody-mediated rejection (ABMR) in Banff classification since 2003. However, the sensitivity and specificity of C4d staining have been questioned, and recently, C4d-negative ABMR has been more focused in renal allograft pathology. The aim of this study was to make certain of C4d staining for ABMR that was diagnosed by clinical and morphological findings. C4d staining was employed by immunofluorescence. This study included 14 patients with acute ABMR and 16 with chronic active ABMR. Eight of acute ABMR were ABO-blood-type-incompatible renal transplantation (ABOinRTx) pre-treated by DFPP and splenectomy or rituximub. In acute ABMR after ABOinRTx, C4d staining along peritubular capillary (PTC) was positive in five of them (62.5%). Only one graft biopsy of five acute ABMR with donor-specific antibody (DSA) showed C4d positive. We assembled 16 graft biopsies showing typical transplant glomerulopathy and thickened PTC basement membrane with peritubular capillaritis as a suspicious pathological chronic active ABMR. Four of eight DSA-positive patients were C4d negative in PTC; however, three of four DSA-positive and C4d-negative patients in PTC chronic active ABMR were C4d positive in only glomerular capillaries. C4d positivity could not come to a specific marker of ABMR diagnosing based on clinically and ordinary morphological findings.