TY - JOUR
T1 - The clinical and molecular significance of C4d staining patterns in renal allografts
AU - Hayde, Nicole
AU - Bao, Yi
AU - Pullman, James
AU - Ye, Bin
AU - Calder, Brent R.
AU - Chung, Monica
AU - Schwartz, Daniel
AU - Alansari, Ahmed
AU - De Boccardo, Graciela
AU - Ling, Min
AU - Akalin, Enver
PY - 2013/2/27
Y1 - 2013/2/27
N2 - 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.
AB - 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.
KW - C4d
KW - Donor-specific anti-HLA antibodies
KW - Gene expression
KW - Microarrays
UR - http://www.scopus.com/inward/record.url?scp=84874665838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874665838&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e318277b2e2
DO - 10.1097/TP.0b013e318277b2e2
M3 - Article
C2 - 23274969
AN - SCOPUS:84874665838
SN - 0041-1337
VL - 95
SP - 580
EP - 588
JO - Transplantation
JF - Transplantation
IS - 4
ER -