Abstract: FR-PO215

Gene Expression Analysis of Active and Chronic Renal Lesions in IgA Nephropathy Diagnosed Using the MEST-C Classification: A Multicenter Study

Session Information

Category: Cell Biology

  • 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation

Authors

  • Cox, Sharon N., University of Bari, Bari, Italy
  • Gangemi, Concetta, AOUI verona, Verona, Italy
  • Schena, Francesco Paolo, University of Bari, Bari, Italy
  • Curci, Claudia, University of Bari, Bari, Italy
  • Serino, Grazia, IRCCS "S de Bellis", Castellana Grotte, Bari, Italy
  • Rossini, M., University of Bari, Department of Emergency and Organ Transplantation, Nephrology Unit, Bari, Italy
  • Bonomini, Mario, University of Chieti, Chieti, Italy
  • Sirolli, Vittorio, clinical nephrology university of chieti, Chieti, Italy
  • Felaco, Paolo, Clinical of Nephrology, University G.d'Annunzio Chieti, Francavilla al Mare, Italy
  • Zaza, Gianluigi, University of Verona, Verona, Italy
  • Squarzoni, Isabella, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
Background


The diagnosis of idiopathic IgA Nephopathy (IgAN) is based on the “split system” where 4 types of renal lesions are scored: Mesangial hypercellularity (M 0-1), Endocapillary hypercellularity (E 0-1), Segmental glomerulosclerosis (S 0-1) and Tubular atrophy/interstitial fi brosis (T 0-2). Recently an extension of the MEST score has been suggested introducing crescents (C 0-2) in the split system because this lesion, together with E, are predictive of outcome (Trimarchi H et al KI ,2017). Aim of our study was to identify specific gene expression changes that characterize active renal lesions (E and C) that may be more responsive to immunosuppressive therapy and chronic lesions (S and T).

Methods

Total RNA was extracted from archival FFPE renal tissue samples of 52 IgAN patients, 24 non-IgAN patients (Minimal change 12, membranous nephropathy 12) and 7 kidney living donors (controls). Genome-wide gene expression profiles were generated and Oneway ANOVA with tukeyHSD post hoc testing was used to identify specific transcripts associated with active and chronic lesions in IgAN. Real Time PCR was used for validation of the identified transcripts.

Results

We identified 391 genes exclusively modulated in IgAN biopsies with active lesions, 35 were down regulated and 355 were up-regulated. Some genes were specifically involved in glomerular injury. These genes belonged to renal cellular damage and immune system regulatory pathways. Moreover, we identified 194 genes that were differentially modulated in IgAN characterized by chronic lesions, 78 were down regulated and 116 were up-regulated. Candidate transcripts were validated by qRT-PCR in an extended cohort of IgAN biopsies.

Conclusion

Transcriptomics on FFPE renal biopsies integrates histomorphologic renal lesions. Our study identifies specific gene expression changes involved in active and chronic lesions at the time of renal biopsy. We are using system pharmacology on these genes to identify targeted molecules able to revert aberrant expression networks characterizing active and chronic lesions.

Funding

  • Government Support - Non-U.S.