K.A. Sablik, N.H.R. Litjens, A.M.A. Peeters, M.C. Clahsen-van Groningen, M. Klepper, M.G.H. Betjes
Wednesday 13 march 2019
14:02 - 14:04h at Koningin Máximazaal
Categories: Basaal, Parallelsessie
Parallel session: Parallelsessie III - Basaal I
Background: Chronic-active antibody mediated rejection (c-aABMR) is the leading cause of long-term renal allograft loss. Fc-receptor CD16 bearing natural killer (NK) cells may be involved in mediating renal endothelial cell damage in c-aABMR. A single nucleotide polymorphism within CD16 gene, i.e. the GG- but not the GT- or TT-genotype, is associated with increased CD16 expression and function of NK cells. The GG-genotype could therefore be a risk factor for developing c-aABMR. This study investigated NK cells and their CD16 expression in cases of c-aABMR.
Methods: Cases of c-aABMR in renal allografts (N=148) and controls (N=137, kidney transplant recipients without c-aABMR) were genotyped for the G or T allele of the CD16 gene. Frequencies of circulating NK cells and their expression of CD16 were measured in 25 cases of c-aABMR and compared to matched controls of kidney transplant recipients. Furthermore, the presence of NK cells in renal biopsies of 20 c-aABMR cases (CD3-CD57+cells) was studied.
Results: The allelic distribution of the GG, GT and TT-genotype within CD16 was respectively, 16%, 41% and 43% for c-aABMR cases and 13%, 39% and 48% for controls (p=0.73).
Individuals with TT had the lowest expression of CD16 on their circulating NK cells (median MFI 3.7 x104) compared to GT (median MFI 6.3 x104) and GG (median MFI 5.8 x104), (p=0.01). In addition, the % of CD16+NK cells was lowest in the TT group (median 80% vs 93% and 87%, p=0.02).
However, independent of T/G genotype, cases with c-aABMR showed a significantly higher expression of CD16 on their circulating NK compared to the matched controls (p=0.01). Frequencies of NK cells were similar between both groups.
NK cells in renal biopsies of c-aABMR cases were absent in glomeruli in 40% of the cases and present at low numbers in the remaining 60% of cases. NK cells were observed in the interstitium but at low numbers (<5% of infiltrating cells).
Conclusions: Cases of c-aABMR have a significant higher expression of CD16 on circulating NK cells which cannot be explained by a difference in allelic distribution pattern for the T/G variants within the CD16 gene. NK cells are rarely found in kidney biopsies of c- aABMR patients suggesting that an ephemeral interaction between NK cells and renal endothelial cells may explain the increased CD16 expression.