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Abstract: FR-PO876

CYP4F11 - A Potential Marker of Accommodation in ABO-Incompatible Renal Transplant Biopsies

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Roufosse, Candice A., Imperial College London, London, United Kingdom
  • Cook, H. Terence, Imperial College of London, London, United Kingdom
  • Willicombe, Michelle, Imperial College London, London, United Kingdom
  • Cairns, Tom, IMPERIAL COLLEGE HEALTHCARE, LONDON, United Kingdom
  • Galliford, Jack W., IMPERIAL COLLEGE HEALTHCARE, LONDON, United Kingdom
  • Toulza, Frederic Jb, Imperial College London, London, United Kingdom
  • Dominy, Kathy M., Imperial College London, London, United Kingdom
Background

Recipients of an ABO incompatible transplant have circulating anti-AB antibodies, A and/or B antigens expressed on endothelium and usually C4d deposition on the endothelium, yet this seldom leads to antibody-mediated rejection. It has been hypothesised that this is related to upregulation of complement regulator and/or anti-apoptotic transcripts. We sought to identify differentially expressed genes between ABO-incompatible (ABOi) and ABO-compatible (ABOc) surveillance biopsies with normal histology.

Methods

RNA sequencing was performed to identify differentially expressed genes between 4 ABOi and 4 ABOc surveillance biopsies with normal histology. Differential expression was validated using RNA from formalin-fixed paraffin-embedded tissue from 14 ABOi and 80 ABOc renal transplant patients, using a Nanostring nCounter custom panel.

Results

RNA sequencing identified a number of differentially expressed genes. None of the complement regulator and/or anti-apoptotic genes were upregulated in ABOi samples. Eighteen genes considered the top hits in sequencing analysis were validated using a Nanostring nCounter custom panel. The only differentially expressed gene that was confirmed was CYP4F11, which was reduced in ABOi biopsies (p=0.001, Mann-Whitney test) (See figure 1).

Conclusion

Genes classically hypothesised to be up-regulated in ABOi transplants were not found to have differential expression. Expression of cytochrome p450 4F11 isoform (CYP4F11) is reduced in ABOi patients. Most of the substrates of cytochrome p450 4F isoforms are eicosanoids, which play important roles in the inflammatory response. Down-regulation of CYP4F11 in ABOi transplants may be be playing a role in accommodation to the anti-A or B antibodies and the presence of complement on the endothelial cell surface. .