Poster 25. Increased number of intragraft FOXP3+ T cells is strongly correlated with decreased graft survival in chronic-active antibody-mediated rejection

Thursday 14 march 2019

12:57 - 13:00h

Categories: Klinisch, Postersessie

Parallel session: Postersessies 5 - Clinical

K.A. Sablik1, E.S. Jordanova2, M.C. Clahsen-van Groningen3, M.G.H. Betjes1

1Dept. of Internal Medicine, Division of Nephrology and Kidney Transplantation, 2Dept. of Oncological Gynaecology, 3Dept. of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Chronic-active antibody-mediated rejection (c-aABMR) is the most important cause of late renal allograft failure. However, renal inflammation and rate of loss of renal allograft function vary substantially. Surprisingly, little is known about the type of immune cell infiltrates in the kidney during c-aABMR and whether this correlates with graft survival. In this study, various immune cell subpopulations in renal biopsies of patients with c-aABMR were quantitatively characterized and correlated with allograft survival.

Methods: Multiplex immunofluorescent staining was performed on 20 cases of biopsy-proven c-aABMR. The stainings were designed to identify T cell subsets (CD3, CD8, Foxp3 and granzyme B), macrophages (CD68 and CD163), B cells (CD20) and NK cells (CD57). The number of positive cells were counted in the glomeruli (cells/glomerulus) and the tubulo-interstitial (TI) compartment (cells/HPF).

Results: CD3+T cells were the dominant cell type in both glomeruli and the TI compartment. The glomeruli had a mean total of 5.5 CD3+cells, 62% being CD8+T cells. Forty-six percent of CD8+T cells were positive for granzyme B. Macrophages had a mean of 4 cells per glomerulus, of which 68% were pro-fibrotic M2 macrophages (CD68+CD163+).

The TI compartment showed a mean of 116 CD3+cells per HPF, of which 46% were CD4+and 54% CD8+. Macrophage count was 21.5 per HPF with 39% being of M2 type (CD68+CD163+). CD20+cells were sporadically present in glomeruli, whereas 45% of biopsies showed B cell aggregates in the TI compartment. NK cells were rarely present in the glomeruli and scarcely in the TI compartment.

Remarkably, decreased graft survival was significantly associated with increased numbers of CD3+FoxP3+cells in the TI compartment (p=0.004) and a trend towards increased amount of macrophages (CD68+) in the TI compartment (p=0.08).

Conclusions: Renal allograft biopsies with c-aABMR have differential compartmentation of infiltrating immune cells with a predominance of CD8+T cells. Interestingly, increased numbers of FoxP3+T cells in the TI compartment are associated with inferior allograft survival.