Kidney Week

Abstract: FR-PO877

C4d Positive Renal Transplant Biopsies with No Other Evidence of Rejection: A Transcript Expression Investigation Using NanoString nCounter Technology

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Roufosse, Candice A., Imperial College, London , United Kingdom

Candice A. Roufosse,

• Willicombe, Michelle, Imperial College of London, London, United Kingdom

Michelle Willicombe,

• Beckwith, Hannah K.S., Imperial College of London, London, United Kingdom

Hannah K.S. Beckwith,

• Cairns, Tom, Imperial College Healthcare NHS Trust, London, United Kingdom

Tom Cairns,

• Goodall, Dawn, Imperial College Healthcare NHS Trust, London, United Kingdom

Dawn Goodall,

• Brookes, Paul, Imperial College Healthcare NHS Trust, London, United Kingdom

Paul Brookes,

• Cook, H. Terence, Imperial College of London, London, United Kingdom

H. Terence Cook,

• Dominy, Kathy M., Imperial College London, London, United Kingdom

Kathy M. Dominy,

Background

Immunohistochemical staining for C4d in peritubular capillaries has been part of antibody-mediated rejection (AbMR) definition in the Banff Classification for Allograft Pathology since 2003. However, with limited sensitivity and specificity, the clinical significance of C4d-positive biopsies without evidence of rejection (C4d+ WER) is unknown. We investigated the molecular significance of C4d positivity in such biopsies from both ABO-compatible and incompatible renal transplant patients.

Methods

RNA was extracted from formalin-fixed paraffin-embedded renal transplant biopsies (n=125) and gene expression analysis of 35 AbMR-associated transcripts carried out using the NanoString nCounter system.

Results

AbMR-associated transcripts were significantly increased in samples with AbMR or suspicious for AbMR. A subgroup of 17/35 transcripts that best distinguished AbMR from C4d-negative biopsies without evidence of rejection was used to study C4d+ WER samples. There was no differential expression between C4d negative and C4d positive biopsies WER from both ABO incompatible and compatible transplants.
The geometric mean of 17 differentially expressed genes was used to assign the C4d+WER biopsies a high- or low-risk score for AbMR. Follow-up biopsies showed AbMR within 1 year of initial biopsy in 5/7 high-risk patients but only 2/46 low-risk patients.
In multivariate logistic regression analysis, elevated transcript levels in a C4d+ WER biopsy were associated with increased odds for biopsy-proven AbMR on follow-up (p=0.032, odds ratio 16.318), whereas factors including DSA status and time from transplant to biopsy were not.

Conclusion

Gene expression analysis in C4d+WER samples has the potential to identify patients at risk of imminent AbMR.