Background: Intragraft gene expression profiles of glomerular disease after kidney transplantation has not been well described other than transplant glomerulopathy (TGP) which develops due to chronic rejection. We aimed to evaluate intragraft gene expression profiles of post-transplant glomerular disease including membranous glomerulopathy, secondary or primary/collapsing focal segmental glomerulosclerosis (FSGS), comparing to normal biopsies using microarrays.

Methods: The gene expression profiles of the 83 kidney biopsy specimens were studied by Affymetrix HuGene 1.0 ST expression arrays. TGP (n=33), membranous nephropathy (n=10), secondary/late FSGS (n=16), and primary/collapsing FSGS (n=6) were compared to normal transplant kidney biopsies (n=16).

Results: As expected, transplant glomerulopathy biopsies had increased expression of gamma interferon and rejection (GRIT), cytotoxic T-cell (CAT) associated pathogenesis based gene transcripts and donor-specific antibody associated gene transcripts (DSAST). However, other glomerular diseases had intragraft gene expression profiles with increased GRIT, CAT and also constitutive macrophage (CMAT), Alternate Macrophage (AMA) but not DSAST. B-cell (BAT), natural killer cell (NKAT) and endothelial cell associated (ENDAT) gene transcripts observed in only primary/collapsing FSGS biopsies. GeneOntologyanalysisshowed that all 4 groups had increased expression of gene transcripts related to activation, regulation, and differentiation of T cells, B cells, leukocytes, cytokines, chemokines, chemotaxis, and immune response compared to normal biopsies. Ingenuity Pathways Analysis demonstrated majorly overlapping differentially expressed genes between different comparisons indicating majorly common pathways and gene expression.

Conclusions: Post-transplant glomerular disease including membranous glomerulopathy and FSGS had intragraft gene transcripts similar to rejection associated gene transcripts and share overlapping gene transcripts with transplant glomerulopathy.

CITATION INFORMATION: Akalin E., e Silva M., Bao Y., Bontha V., Ajaimy M., Mas V., [Oacute] Broin P. Molecular Assessment of Post-Transplant Glomerular Disease Comparing to Transplant Glomerulopathy Am J Transplant. 2017;17 (suppl 3).

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