Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity

Transplantation Direct, vol. 9, pp. e1480

Abstract

Background. Mast cells are potential contributors to chronic changes in kidney transplants (KTx). Here, the role of mast cells (MCs) in KTx is investigated in patients with minimal inflammatory lesions. Methods. Fourty-seven KTx biopsies (2009–2018) with borderline pathological evidence for T cell-mediated rejection according to the Banff’17 Update were retrospectively included and corresponding clinical data was collected. Immunohistochemistry for tryptase was performed on formalin-fixed paraffin-embedded sections. Cortical MCs were counted and corrected for area (MC/mm²). Interstitial fibrosis was assessed by Sirius Red staining and quantified using digital image analysis (QuPath). Results. Increased MC number was correlated to donor age (spearman’s r = 0.35, P = 0.022), deceased donor kidneys (mean difference = 0.74, t [32.5] = 2.21, P = 0.035), and delayed graft function (MD = 0.78, t [33.9] = 2.43, P = 0.020). Increased MC number was also correlated to the amount of interstitial fibrosis (r = 0.42, P = 0.003) but did not correlate with transplant function over time (r = −0.14, P = 0.36). Additionally, transplant survival 2 y post-biopsy was not correlated to MC number (mean difference = −0.02, t [15.36] = −0.06, P = 0.96). Conclusions. MC number in suspicious (borderline) for acute T cell-mediated rejection is correlated to interstitial fibrosis and time post-transplantation, suggesting MCs to be a marker for cumulative burden of tissue injury. There was no association between MCs and transplant function over time or transplant survival 2 y post-biopsy. It remains unclear whether MCs are just a bystander or have pro-inflammatory or anti-inflammatory effects in the KTx with minimal lesions.

Authors 10

1. Hilal Varol corresponding

   Erasmus MC · Erasmus MC Transplant Institute

   Affiliation as printed

   Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands

   Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

2. G. van der Elst

   Erasmus MC

   Affiliation as printed

   Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands

3. Carla C. Baan

   Erasmus MC · Erasmus University Rotterdam · Erasmus MC Transplant Institute

   Affiliation as printed

   Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

   Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

4. Myrthe van Baardwijk

   Erasmus MC

   Affiliation as printed

   Companion Diagnostics and Personalised Healthcare, Omnigen BV, Delft, Netherlands

   Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands

5. Dennis Alexander Hesselink

   Erasmus MC · Erasmus University Rotterdam · Erasmus MC Transplant Institute

   Affiliation as printed

   Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

   Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

6. Jean–Paul Duong Van Huyen

   Assistance Publique – Hôpitaux de Paris · Hôpital Necker-Enfants Malades

   Affiliation as printed

   Department of Pathology, Necker Hospital, APHP, Paris, France

7. Rafael Kramann Aachen Division of Nephrology and Clinical Immunology Department of Experimental Medicine and Systems Biology

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany

   Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany

8. Marion Rabant

   Assistance Publique – Hôpitaux de Paris · Hôpital Necker-Enfants Malades

   Affiliation as printed

   Department of Pathology, Necker Hospital, APHP, Paris, France

9. Thierry P. P. van den Bosch

   Erasmus MC

   Affiliation as printed

   Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands

10. Marian C. Clahsen‐van Groningen Aachen Department of Experimental Medicine and Systems Biology

    RWTH Aachen University · Erasmus MC · Erasmus MC Transplant Institute

    Affiliation as printed

    Department of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany

    Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands