The clinical and molecular significance of C4d staining patterns in renal allografts

Nicole Hayde, Yi Bao, James Pullman, Bin Ye, Brent R. Calder, Monica Chung, Daniel Schwartz, Ahmed Alansari, Graciela De Boccardo, Min Ling, Enver Akalin

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Background: We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Methods: Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays. Results: Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P<0.001). The glomerulitis, interstitial inflammation, and peritubular capillaritis scores were also significantly higher in minimal (0.88, 1.25, and 1.5) and focal/diffuse PTC C4d+ biopsies (0.65, 1.41, and 1.5), compared with C4d-negative biopsies (0.25, 079, and 0.34), respectively. There were no differences in the DSA frequency, AMR rate, or Banff scores between isolated glomerular C4d+ and C4d-negative patients. Although both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, interferon-gamma and rejection-induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis-based transcripts, there was no activation of immune-response- related genes in isolated glomerular C4d+ biopsies. CONCLUSION: Minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR, circulating DSAs and immune-response-related gene activation.

Original languageEnglish (US)
Pages (from-to)580-588
Number of pages9
Issue number4
StatePublished - Feb 27 2013


  • C4d
  • Donor-specific anti-HLA antibodies
  • Gene expression
  • Microarrays

ASJC Scopus subject areas

  • Transplantation


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