Immunomics of Renal Allograft Acute T-Cell Mediated Rejection Biopsies of Tacrolimus- and Belatacept- Treated Patients

M. van der Zwan¹, C. C. Baan¹, R. C. Colvin², R. N. Smith², R. A. White², D. N. Ndishabandi², A. L. Nigg¹, T. P. van den Bosch¹, G. N. de Graav¹, M. C. Clahsen-van Groningen¹, D. A. Hesselink¹

¹Internal Medicine, Division Nephrology and Transplantation, Erasmus MC, Rotterdam, Netherlands, ²Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA

Meeting: 2019 American Transplant Congress

Abstract number: A7

Keywords: Gene expression, Histology

Session Information

Session Name: Poster Session A: Acute Rejection

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Belatacept-based therapy in kidney transplant recipient has been shown to increase long-term renal allograft and patient survival compared with calcineurin inhibitor based therapy, however with an increased risk of acute T cell-mediated rejection (aTCMR). An improved understanding of co-stimulation blockade resistant rejections could lead to a more personalized approach to belatacept therapy. Here, immunomic profiles of aTCMR biopsies of patients treated with either tacrolimus or belatacept were compared.

*Methods: Formalin-fixed paraffin-embedded (FFPE) renal transplant biopsies were used for immunohistochemistry, and gene expression analysis using the innovative NanoString technique. To validate NanoString, transcriptomic profiles of patients with and without biopsy-proven aTCMR were compared. Biopsies from 31 patients were studied: 14 tacrolimus-treated patients with aTCMR, 11 belatacept-treated patients with aTCMR, and 6 controls without rejection.

*Results: A distinct pattern was seen in biopsies with aTCMR compared to negative controls: 78 genes had a higher expression in the aTCMR group (FDRPV<0.05 to 1.42e-05). The most significant were T cell-associated genes (CD3, CD8, and CD4; p<1.98e-04), γ-interferon-inducible genes (CCL5, CXCL9, CXCL11, CXCL10, TBX21; p<1.33e-04) plus effector genes (GNLY, GZMB, ITGAX; p<2.82e-03). Immuno-phenotypical analysis of the classic immune markers of the innate and adaptive immune system was comparable between patients treated with either tacrolimus or belatacept. In addition, the transcriptome of both groups was similar.

*Conclusions: No difference was found in immunomics of aTCMR biopsies of tacrolimus- and belatacept-treated patients. This suggests that clinically-diagnosed aTCMR reflects a final common pathway of allo-recognition which is unaffected by the type of immunosuppressive therapy.

To cite this abstract in AMA style:

Zwan Mvander, Baan CC, Colvin RC, Smith RN, White RA, Ndishabandi DN, Nigg AL, Graav GNde, Groningen MCClahsen-van, Hesselink DA. Immunomics of Renal Allograft Acute T-Cell Mediated Rejection Biopsies of Tacrolimus- and Belatacept- Treated Patients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/immunomics-of-renal-allograft-acute-t-cell-mediated-rejection-biopsies-of-tacrolimus-and-belatacept-treated-patients/. Accessed May 11, 2025.

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