2002 E. Mead Johnson Award for Research in Pediatrics Lecture: the molecular biology of the anemia of chronic disease: a hypothesis.
The anemia of chronic disease is a common disorder that afflicts patients with a wide variety of inflammatory conditions including arthritis, malignancies, infections, and inflammatory bowel disease. It results in significant morbidity and may be severe enough to require blood transfusions. The pathogenesis of anemia of chronic disease is not fully understood, but poor maintenance of red blood cell mass has been observed at three levels: 1) iron is not efficiently recycled from reticuloendothelial macrophages to erythroid precursors, 2) erythroid precursors respond poorly to erythropoietin, and 3) red blood cell survival is decreased. Whether each of these changes is related to the same effector of the inflammatory process is unknown. We have had the opportunity to investigate severe anemia of chronic disease in an unusual group of patients with glycogen storage disease type 1a. We found that anemia was directly related to the presence of large hepatic adenomas that inappropriately produced a new peptide hormone, hepcidin. Hepcidin has recently been identified as part of the innate immune response and is a key regulator of cellular iron egress. Based on our findings in this patient group, we propose a central role for hepcidin in anemia of chronic disease, linking the inflammatory process with iron recycling and erythropoiesis. We present a hypothesis based on our findings.
Roy
Cindy N
CN
Children's Hospital Boston, MA 02115, USA.
Weinstein
David A
DA
Andrews
Nancy C
NC
D000236:Adenoma / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D000740:Anemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D002648:Child; D002908:Chronic Disease; D005953:Glycogen Storage Disease Type I / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D007501:Iron