Background: Transplant glomerulopathy (TGP) is frequently found in the setting of chronic antibody mediated rejection along with microvascular inflammation (MVI) (peritubular capillaritis+glomerulitis score > 1) and/or positive c4d staining. We aimed to assess the molecular profiles of TGP in the absence of microvascular inflammation and c4d staining as compared to TGP with positive MVI and/or C4d.

Methods: A total of 42 for-cause renal allograft biopsies were studied using Affymetrix HuGene 1.0 ST expression arrays; 12 with normal biopsy findings (G1), 17 with a diagnosis of TGP, c4d positive and/or a MVI score >1 (G2), and 13 with a diagnosis of TGP and MVI score </=1 and C4d negative (G3).

Results: There was no difference in sex, race, or type of transplant between the 3 groups. More patients in both TGP groups, G2 (82.4%) and G3 (69.2%) had PRA >20% at the time of biopsy compared to those in G1 (25%), p=0.006 and p=0.05 respectively. More patients had DSA in G2 (TGP with MVI or C4d), 82.4%, as compared with G1 (8.3%) p<0.001 and G3 (TGP without MVI or C4d), 38.4%, p=0.02. Pathogenesis based transcripts revealed increased expression of gamma interferon and rejection (GRIT) and DSA associated transcripts (DSAST) seen in antibody-mediated rejection when G2 (TGP with MVI or C4d) were compared to G1 and G3 (TGP without MVI or C4d) groups (Table 1). However, when G3 (TGP without MVI or C4d) compared to G1, increased expression of Cytotoxic T cell (CAT), T-regulatory cell (TREG), and B cell associated transcripts (BAT) were observed but not GRIT or DSAST. There was no difference in expression of natural killer cell and endothelial cell associated transcripts between the 3 groups.

Conclusions: Gene expression profiles of TGP in the absence of microvascular inflammation and C4d involve an upregulation of T cell mediated responses but not transcripts seen in antibody mediated rejection suggesting that this subset may represent chronic T cell mediated rejection.

CITATION INFORMATION: Lubetzky M, O Broin P, Bao Y, Akalin E. Molecular Significance of Microvascular Inflammation and C4d Negative Transplant Glomerulopathy. Am J Transplant. 2016;16 (suppl 3).

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