Up-regulation of Duffy antigen receptor expression in children with renal disease

The Duffy antigen chemokine receptor (DARC) is a promiscuous chemokine receptor that binds chemokines from the C-X-C and C-C families. DARC was initially described on red blood cells, but subsequent studies have demonstrated DARC protein expression on renal endothelial and epithelial cells, even in Duffy-negative individuals whose red cells lack DARC. Because approximately 68% of African Americans lack the Duffy/DARC on their red cells, we carried out experiments to identify the specific renal cells expressing DARC protein and mRNA in African American children and to define whether DARC expression was altered in renal inflammatory processes.

Immunohistochemistry and in situ hybridization studies were done in 28 renal sections from children with each of the following diagnoses: HIV nephropathy (HIVAN), HIV-associated hemolytic uremic syndrome (HIV-HUS), HIV infection without renal disease, HIV-negative children without renal disease, and Argentinean children with classic HUS.

The predominant localization of DARC mRNA and protein was found in endothelial cells underlying postcapillary renal venules in all patients studied. However, DARC mRNA and protein were significantly up-regulated in peritubular and glomerular capillaries, collecting duct epithelial cells, and interstitial inflammatory cells in children with HIVAN, HIV-HUS, and classic HUS.

These findings support the notion that the renal DARC is linked to the inflammatory cascade and that African American children may be at risk of accumulating chemokines in renal tissues.