American Journal of Hematology 37:247-252 (1 991) z Expression of Transferrin Receptors on Monocytes in Hemochromatosis Paul C. Adams, Luan A. Chau, Martin White, and Andrew Lazarovits Department of Medicine, University Hospital, University of Western Ontario, London, Ontario, Canada To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosispatients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = -0.59, zyx P < -02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = -0.90, P < .001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochro- matosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expres- sion in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non-transferrin iron metabolism, including ferritin, requires further investigation in the zyxwvut RE cell in hemochromatosis. Key words: iron, reticuloendothelial system INTRODUCTION zyxwvutsrq Hemochromatosis is a genetic disease of unknown cause in which iron is deposited in the liver, pancreas, heart, and other organs leading eventually to organ dysfunction. Receptor-mediated uptake of transferrin iron has been demonstrated to be a major pathway of iron uptake into many cells [I] and previous studies have demonstrated down-regulation of the transferrin receptor in response to iron loading in liver, intestine, fibroblasts, and tumor cell lines [2-51. Conflicting reports have described the down-regulation [6-91 and the paradoxical up-regulation [ 10,111 of the transferrin receptor in re- sponse to iron loading in monocytes and macrophages. The reticuloendothelial (RE) cells in hereditary hemo- chromatosis have a relative paucity of iron, which has raised the possibility of a basic defect in RE cell in hemochromatosis [12]. In this study the expression of transferrin receptor on circulating monocytes and its relationship to body iron stores was studied in hereditary hemochromatosis, and in normal volunteers. zyxwvu 0 1991 Wiley-Liss, Inc. MATERIALS AND METHODS Patient Population The diagnosis of hereditary hemochromatosis in 14 patients was based on marked parenchymal iron loading on microscopic examination of a liver biopsy, hepatic iron concentration, and family investigations with no other obvious cause of iron loading. Patients included proband cases and asymptomatic discovered cases within families. Antibody binding studies, serum ferritin, and hepatic iron concentration was performed within 1 month of the diagnosis of hemochromatosis prior to the institu- tion of venesection therapy. Normal subjects included 14 volunteers with no evidence of iron overload and a normal serum ferritin. Serum ferritin was measured using Received for publication August 15, 1990; accepted March 14, 1991. Address reprint requests to Dr. Paul C. Adams, Department of Medicine, University Hospital, P.O. zyxw Box 5339, London, Ontario N6A 5A5, Canada.