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Abstract: TH-PO1111

Urinary CXCL9 Levels Correlate with Quantitative Tubulitis in Kidney Allograft Biopsies

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Delsante, Marco, Universita di Parma, Parma, Italy
  • Gandolfini, Ilaria, Universita di Parma, Parma, Italy
  • Diblasi, Ilaria, Universita di Parma, Parma, Italy
  • Pilato, Francesco Paolo, Universita di Parma, Parma, Italy
  • Campanini, Nicoletta, Universita di Parma, Parma, Italy
  • Rossi, Giovanni maria, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Bagnasco, S.M., The Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Maggiore, Umberto, Universita di Parma, Parma, Italy
  • Rosenberg, Avi Z., The Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Fiaccadori, Enrico, Universita di Parma, Parma, Italy
Background


Acute and chronic cell mediated rejection (CMR) are histologically characterized by the presence of interstitial inflammation (i) and tubulitis (t), with or without endarteritis, as defined by Banff Classification system [Haas M, et al. AJT, 2018]. The Banff tubulitis score (t) is semi-quantitative, based on the most inflamed tubular profile. These values are then used to establish the grade of CMR. Tubulitis can be difficult to assess using standard staining, and its interobserver reproducibility is poor. Urinary CXCL9 has been shown to correlate with the diagnosis of CMR, and their levels decrease after successful therapeutic interventions [Gandolfini I, et al. KI Rep, 2017]. We used immunohistochemical CD3 stain with a PAS counterstain to elicit a continuous quantitative tubulitis score in kidney allograft biopsies and correlated the findings with urinary CXCL9 levels (Figure 1).

Methods


On digitized whole slide images of CD3+PAS slides (n=12; CMR = 5 biopsies, borderline lesions= 1 and no rejection=6) mean CD3+ cells per tubule (mCD3/t), percentage of tubules showing at least 1 CD3+ cells (tubulitis ratio, tr) and number of CD3+ cells in the most inflamed tubule (maxt) were manually assessed using ViewPoint software (PreciPoint). Urinary CXCL9 levels at the time of diagnosis were measured using ELISA kit (R&D, Quantikine ELISA). Prism GraphPad 5 was used for statistical analysis.

Results


We found significant correlation between urinary CXCL9 levels and mCD3/t (r2 0.75, p=0.0003), tr (r2 0.66, p=0.0012) and maxt (r2 0.70, p=0.0006).

Conclusion


CD3+PAS stain augments current approach’s by generating a continuous score quantify tubulitis. This quantification correlates with urinary CXCL9 levels, a biomarker of CMR. Studies on larger cohorts are underway to better establish the clinical significance and utility of quantitative tubulitis evaluation.