Background: We investigated the histopathologic features and gene expression profiles of C4d-/donor-specific anti-HLA antibodies (DSA)+ and C4d-/DSA- transplant glomerulopathy (TGP) biopsies compared to C4d+/DSA+ chronic antibody-mediated rejection (AMR) and non-specific interstitial fibrosis and tubular atrophy (IFTA).
Methods: 263 kidney transplant biopsies were included in the study. Gene expression profiles of 48 biopsies were studied by Affymetrix HuGene 1.0 ST expression arrays.
Results: 18 biopsies showed CAMR, 14 C4d-/DSA+ TGP, 25 C4d-/DSA- TGP and 47 had non-specific IFTA. There were no significant differences in the demographics. The mean glomerulitis (g) score was higher in CAMR (0.72) and DSA+ & DSA- TGP (0.64, 0.48) compared to IFTA (0.06; p= 0.008) but the peritubular capillaritis (ptc) score was higher in CAMR (1.39) and C4d-/DSA+ TGP (1.07) but not C4d-/ DSA-TGP (0.25) and IFTA (0.21; p<0.001). The sum g+ptc score gradually increased from IFTA (0.28) to C4d-/DSA- TGP (0.75), C4d-/DSA+/TGP (1.71) and C4d+/DSA+ CAMR (2.11); p<0.001. Gene expression profiles of 17 IFTA (G1), 8 C4d-/DSA- TGP (G2), 9 C4d-/DSA+ TGP (G3), and 14 CAMR (G4), were analyzed and the results of Pathogenesis Based Transcripts of Interferon-Gamma and Rejection Induced (GRIT), Quantitative Cytotoxic T-cell (QCAT), Quantitative Constitutive Macrophage (CMAT), B-cell (BAT), Natural Killer Cell (NKAT), Endothelial Cell (ENDAT) associated transcripts and Donor Specific Antibody Selective Transcripts seen in AMR (DSAST) are shown in the Table. While CAMR demonstrated statistically significant upregulation of all GRIT, QCAT, CMAT, BAT, NKAT, ENDAT, and DSAST transcripts and C4d-/DSA+ TGP showed GRIT, QCAT, NKAT, and DSAST transcripts compared to IFTA biopsies, C4d-/DSA- TGP samples showed only increased QCAT transcript expression.
Conclusion: Our results indicate that ptc is a more specific finding of CAMR than C4d+ staining. C4d-/DSA+ TGP showed similar gene expression profiles to CAMR biopsies. C4d-/DSA- TGP biopsies had a higher g score without ptc and increased QCAT expression indicating an heightened cellular immune response.
To cite this abstract in AMA style:Hayde N, Bao Y, Pullman J, Boccardo GDe, Lubetzky M, Akalin E. Intragraft Gene Expression Profiles of C4d-/DSA+ and C4d-/DSA- Transplant Glomerulopathy Biopsies Compared to Biopsies with Chronic Antibody Mediated Rejection [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/intragraft-gene-expression-profiles-of-c4d-dsa-and-c4d-dsa-transplant-glomerulopathy-biopsies-compared-to-biopsies-with-chronic-antibody-mediated-rejection/. Accessed August 12, 2020.
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