Related Experiment Video
Updated: Aug 21, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Peritubular capillary C4d deposition in chronic allograft dysfunction
Hyeon Joo Jeong1, Se Hoon Kim, Yu Seun Kim
1Department of Pathology, Yonsei University College of Medicine, 134 Shinchon- dong, Seodaemun-gu, Seoul 120-752, Korea. jeong10@yumc.yonsei.ac.kr
Insights
Peritubular capillary (PTC) C4d staining indicates acute humoral rejection. In patients with chronic allograft dysfunction, C4d positivity was linked to late acute rejection, not chronic rejection, and showed reduced graft survival.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Peritubular capillary (PTC) C4d staining is a known marker for acute humoral rejection.
- The significance of positive C4d staining in the context of chronic allograft dysfunction remains under-investigated.
Purpose of the Study:
- To investigate the impact of peritubular capillary (PTC) C4d staining on chronic allograft dysfunction.
- To determine the association between C4d positivity and the prevalence of acute and chronic rejection in patients with established chronic allograft dysfunction.
Main Methods:
- Analysis of 93 renal allograft biopsies obtained at least 6 months post-transplantation.
- Immunohistochemical staining using a monoclonal antibody against C4d.
- Correlation of C4d staining results with histological findings of acute and chronic rejection and graft survival rates.
Main Results:
- C4d staining was detected in 17.2% (16/93) of biopsies.
- C4d positivity was associated with a higher proportion of acute rejection (40%) compared to C4d-negative cases (21%).
- No significant difference in the prevalence of chronic rejection or histological injury scores (tubulitis, interstitial inflammation, fibrosis) was observed between C4d-positive and C4d-negative groups.
- The 2-year graft survival rate after biopsy was significantly lower in the C4d-positive group (24.8%) compared to the C4d-negative group (59.0%).
Conclusions:
- C4d staining in peritubular capillaries is associated with late acute rejection in patients with chronic allograft dysfunction.
- C4d staining does not appear to be indicative of chronic rejection based on conventional morphologic criteria.
- Positive C4d staining in this context is linked to poorer long-term graft survival, suggesting its prognostic value beyond acute rejection.
Abstract:
Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.