NIV Congres

In patients, who had been transplanted between 1986 and 1995 and who suffered from acute rejection, a high expression of S100 calcium binding proteins A8 and A9 was found to be associated with favorable graft outcome. We here confirmed this finding in a 1995-2005 transplant cohort: high S100A8 and A9 mRNA expression during acute rejection (>2 times the median; n=36) led to a 12-year graft survival of 91.5%, whereas low expression (n=61) was related to 69.2% graft survival. S100A9 mRNA expression significantly correlated with the extent of S100A9 protein by immunohistochemistry (P<0.005). S100A8 and A9 expression was associated with a significantly elevated expression of anti-inflammatory IL-10 (P<0.01) and regulatory T cell marker FoxP3/CD3 (P<0.0001), and with significantly decreased levels of kidney injury molecule (P<0.05). As S100A8 and S100A9 are mainly expressed by monocytes and macrophages, we investigated protein expression of macrophage activation marker CD163 and pan-marker CD68. Triple immunostaining on paraffin slides showed that the majority of CD68+ macrophages within the tissue were either positive for S100A9 or for the macrophage activation marker CD163, indicating the presence of different macrophage subtypes during acute rejection. In line with the in vivo findings, overexpression of the S100A8 and S100A9 genes in the monocytic cell line THP-1 led to de novo production of IL-10. S100A8 and S100A9 are markers of a distinct macrophage subpopulation during acute transplant rejection, which may have regulatory properties leading to a beneficial graft outcome.