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Abstract: FR-OR141

Gene Expression Profiles of Post-Transplant Glomerular Disease

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Akalin, Enver, Montefiore Medical Center, Bronx, New York, United States
  • Ajaimy, Maria, Montefiore Medical Center, Bronx, New York, United States
  • Bontha, Sai Vineela, University of Virginia, Charlottesville, Virginia, United States
  • Barbachan e Silva, Mariel, National University of Ireland, Galway, Galway, Ireland
  • Ó Broin, Pilib, National University of Ireland, Galway, Galway, Ireland
  • Mas, Valeria, University of Virginia, Charlottesville, Virginia, United States
Background

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

Methods

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

Results

Gene Ontology analysis showed that all 4 glomerular disease 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 (Figure). Comparing canonical pathways the MG was least aggressive in terms of gene expression differences, followed by the secondary/late FSGS when compared to normal allografts. Primary FSGS and TG had the most differentially expressed genes, with most of them involved in inflammatory pathways and immune response. ILK signaling pathway and IL9 signaling pathway were uniquely activated in primary FSGS. All 4 groups demonstrated increased interferon gamma and rejection, cytotoxic T cell and macrophage associated pathogenesis based transcript expression.

Conclusion

Post-transplant glomerular disease including MG and FSGS had intragraft gene transcripts associated with increased immune activity similar to rejection and share overlapping gene transcripts with TG.