C4d and/or immunoglobulins deposition in peritubular capillaries in perioperative graft biopsies in ABO‐incompatible renal transplantation

Abstract

We evaluated 0 h and/or 1 h graft biopsy specimens from 14 recipients in ABO-incompatible renal transplantation using immunofluorescence for C4d, IgG, and IgM. All 0 h biopsy specimens revealed negative C4d, IgG, and IgM deposition in peritubular capillaries (PTC). In contrast, 8 of 14 1 h biopsy specimens revealed a positive C4d deposition in PTC. Eight specimens revealed positive IgM staining and seven of them had both C4d and IgM depositions. Three specimens had C4d, IgM, and IgG depositions in PTC. Three of eight patients with C4d deposition and two of six patients without C4d deposition in the 1 h biopsy group suffered from acute rejection within 1 month of transplantation. These findings suggest that complement fragments and immunoglobulin deposition in PTC in ABO-incompatible renal grafts can start soon after reperfusion, although acute rejection may or may not develop.

Evaluation of Immunosuppressive Regimens in ABO-Incompatible Living Kidney Transplantation—Single Center Analysis

“…We speculate that antibody-mediated immunity occurs in every case with ABO-incompatibility in the early postoperative period, as some described by previous reports of studies that used C4d staining (20). Kanetsuna et al (21) reported that complement fragments and immunoglobulin deposition in peritubular capillaries in ABO-incompatible renal grafts can start soon after reperfusion although acute rejection may or may not develop. However, Park et al (19) describe the normal findings as one of the criteria for identifying accommodated recipients.…”

Pros and cons for C4d as a biomarker

“…However, the fact that more than 70–80% of ABO-incompatible grafts showed diffuse C4d positivity was a surprising finding, especially when compared with the marginal 30–40% diffuse positives observed in the group of patients with a positive cross-match for anti-HLA antibodies. 48-50 …”

Antibody-Mediated Rejection in Renal Allografts

“…This C4d likely reflects the presence of anti-blood group antibody, because we previously observed PTC C4d in only two of 47 1-h postperfusion biopsies, both positives being in recipients who had a positive flow cytometric cross-match for anti-HLA DSA at the time of transplantation and subsequently developed AMR (44). In the study of Kanetsuna et al (43), four of 14 patients, three with C4d on their 1-h postperfusion biopsy and one without, developed AMR during the first 30 d after transplantation. Together, the findings in these studies suggest that in biopsies of ABO-incompatible grafts that are performed for early dysfunction, PTC C4d may be associated with AMR and graft injury, whereas in stably functioning grafts, PTC C4d staining is frequently not associated with AMR and may, as suggested by Platt (45) and Kanetsuna et al (43), reflect graft accommodation.…”

“…In the study of Kanetsuna et al (43), four of 14 patients, three with C4d on their 1-h postperfusion biopsy and one without, developed AMR during the first 30 d after transplantation. Together, the findings in these studies suggest that in biopsies of ABO-incompatible grafts that are performed for early dysfunction, PTC C4d may be associated with AMR and graft injury, whereas in stably functioning grafts, PTC C4d staining is frequently not associated with AMR and may, as suggested by Platt (45) and Kanetsuna et al (43), reflect graft accommodation.…”