Abstract: SA-PO1154
Quantitative Assessment of Active and Chronic Lesions in Renal Allograft Biopsies to Improve Reproducibility, Clinical Correlations, and Outcome Prediction
Session Information
- Transplantation: Clinical - Rejection, Recurrent Disease, Incompatibility
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Delsante, Marco, Università di Parma, Parma, Italy
- Gandolfini, Ilaria, Università di Parma, Parma, Italy
- Bagnasco, S.M., Johns Hopkins University, Baltimore, Maryland, United States
- Maggiore, Umberto, Università di Parma, Parma, Italy
- Fiaccadori, Enrico, Università di Parma, Parma, Italy
- Rosenberg, Avi Z., Johns Hopkins University, Baltimore, Maryland, United States
Background
Banff classification system is based on recognition and scoring of descriptive lesions allowing for pathogenetic classification of rejection. Although expert pathologists readily recognize these lesions, the routine semi-quantitative Banff scoring can be poorly reproducible. Specific immunohistochemical (IHC) stains and new imaging techniques can allow for more precise quantification of tubulitis, interstitial fibrosis (IF) and microvascular inflammation (MVI) (Delsante,TI,2018).
Methods
Tubulitis: we included 12 transplant biopsies of CMR, borderline and no rejection from Parma Hospital (Italy). Analysis of whole slide images of CD3+PAS IHC stained sections allowed for continuous scoring of tubulitis, and results were correlated with urinary CXCL9 levels (a biomarker of cell-mediated rejection). IF: Measuring second harmonic generation (SHG) signal on FFPE unstained kidney section, we assessed collagen deposition in 57 kidney transplant biopsies (Johns Hopkins Hospital-JHH). MVI was quantified in 75 biopsies from JHH using a dual IHC stain (CD34-endothelium and CD45-leukocytes); quantitative scores of peritubular capillaritis and glomerulitis were correlated with donor specific antibodies (DSA) levels and graft outcome
Results
Tubulitis quantitative scores showed significant correlation with urinary CXCL9 levels in patients with histological diagnosis of CMR, borderline lesions or no significant tubular inflammation: mean CD3+ cell per tubule (r2 0.75), tubulitis ratio (r2 0.66) and CD3+ cells is most inflamed tubule (r2 0.70). Measurement of interstitial collagen deposition using SHG outperformed standard Banff score in predicting graft failure hazard(increase 3.87 times per 2SD unit increase of SHG density, 95%CI 1.06-14.16). The use of CD34-CD45 dual stain increased interobserver reproducibility of Banff ptc score and significantly correlated with serum DSA levels and risk of graft loss. In the same cohort, glomerulitis scores showed no correlation with DSA/allograft outcome.
Conclusion
For selected Banff lesions (ptc, t and ci/ct) quantitative measurements can increase clinical correlation compared to semi-quantitative scoring. Quantitative methods are being studied in larger cohorts to confirm clinical and prognostic significance.