When renal allografts turn DARC.

Abstract

The Duffy antigen-receptor for chemokines (DARC) is a chemokine-binding protein that is up-regulated on peritubular capillaries (PTC) during cellular renal allograft rejection. C4d deposition and accumulation of inflammatory cells in PTC are indicators of humoral renal allograft rejection. Because DARC is expressed at the site of C4d deposition and might be involved in inflammatory cell recruitment, the authors evaluated the expression of DARC in different forms of human renal allograft rejection. Deposition of C4d and DARC expression were evaluated by immunohistochemistry in 42 renal transplant biopsy specimens. Biopsy specimens were subdivided according to histologic and immunohistochemical results, that is, C4d-negative biopsy specimens with (Banff 1, n=8) or without signs of cellular rejection (n=16), and C4d-positive biopsies (humoral rejection) with (Banff 1 rejection, n=7) or without cellular rejection (n=11). DARC expression was found on a small number of PTC and veins in patients without rejection. Cellular and humoral rejection led to a comparable increase in the number of DARC-positive PTC (9.7 and 8.7 vs. 2.6 vessels per high-power field [HPF], respectively). The highest numbers were found in biopsy specimens with signs of both humoral and cellular rejection (17.5 vessels per HPF). This is the first study that demonstrates an induction of a chemokine-binding protein at the site of C4d deposition in humoral allograft rejection. The additive effect of humoral and cellular rejection on DARC expression might imply different pathways of DARC induction for different forms of allograft rejection.