Anti-hemojuvelin antibody corrects anemia caused by inappropriately high hepcidin levels

Haematologica

Volumn 101, Issue 5, 2016, Pages e173-e176

  Kovac, Suzana ^a   Böser, Preethne ^b   Cui, Yifang ^b   Ferring Appel, Dunja ^a   Casarrubea, Daniela ^a   Huang, Lili ^b   Fung, Emma ^b   Popp, Andreas ^b   Mueller, Bernhard K ^b   Hentze, Matthias W ^a  

^a EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

^b ABBVIE INC   (United States)

Author keywords

Anemia; Erythroblastic island; Erythropoiesis; Myelodysplastic syndromes; Prognosis

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR; HEMOJUVELIN; HEPCIDIN; INTERLEUKIN 6; MATRIPTASE; MONOCLONAL ANTIBODY; NEOGENIN; SERINE PROTEINASE; HFE2 PROTEIN, MOUSE; HJV PROTEIN, RAT; MEMBRANE PROTEIN;

ANEMIA; BLOOD TRANSFUSION; ENZYME ACTIVITY; ENZYME INHIBITION; ERYTHROPOIESIS; GENE MUTATION; HEMOGLOBIN BLOOD LEVEL; INFLAMMATION; INTESTINE CELL; IRON BLOOD LEVEL; IRON DEFICIENCY ANEMIA; IRON OVERLOAD; LETTER; LIVER CELL; LUCIFERASE ASSAY; MACROPHAGE; NONHUMAN; PROTEIN BINDING; PROTEIN EXPRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; HUMAN; MOUSE; RAT;

ANEMIA; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; HEPCIDINS; HUMANS; MEMBRANE PROTEINS; MICE; RATS;

EID: 84964788505     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2015.140772     Document Type: Letter

References (20)

1. Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta. 2012;1823(9):1434-1443.
2. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38(5):531-539.
3. Niederkofler V, Salie R, Sigrist M, Arber S. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J Neurosci. 2004;24(4):808-818.
4. Samad TA, Srinivasan A, Karchewski LA, et al. DRAGON: a member of the repulsive guidance molecule-related family of neuronal-and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci. 2004;24(8):2027-2036.
5. Mueller BK, Yamashita T, Schaffar G, Mueller R. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system. Philos Trans R Soc Lond B Biol Sci. 2006;361 (1473):1513-1529.
6. Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214-2221.
7. Nissenson AR, Goodnough LT, Dubois RW. Anemia: not just an innocent by stander? Arch Intern Med. 2003;163(12):1400-1404.
8. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008;40(5):569-571.
9. De Falco L, Totaro F, Nai A, et al. Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA). Hum Mutat. 2010;31(5):E1390-1405.
10. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008;8(6):502-511.
11. Nili M, Shinde U, Rotwein P. Soluble repulsive guidance molecule c/hemojuvelin is a broad spectrum bone morphogenetic protein (BMP) antagonist and inhibits both BMP2-and BMP6-mediated signaling and gene expression. J Biol Chem. 2010;285(32):24783-24792.
12. Adamson JW. The anemia of inflammation/malignancy: mechanisms and management. Hematology Am Soc Hematol Educ Program. 2008;159-165.
13. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood. 2010;116(20):4045-4059.
14. Del Vecchio L, Pozzoni P, Andrulli S, Locatelli F. Inflammation and resistance to treatment with recombinant human erythropoietin. J Ren Nutr. 2005;15(1):137-141.
15. De Falco L, Sanchez M, Silvestri L, et al. Iron refractory iron deficiency anemia. Haematologica. 2013;98(6):845-853.
16. Boser P, Seemann D, Liguori MJ, et al. Anti-repulsive Guidance Molecule C (RGMc) Antibodies Increases Serum Iron in Rats and Cynomolgus Monkeys by Hepcidin Downregulation. AAPS J. 2015;17(4):930-8.
17. Theurl I, Schroll A, Sonnweber T, et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood. 2011;118(18):4977-4984.
18. Sasu BJ, Cooke KS, Arvedson TL, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010;115(17):3616-3624.
19. Folgueras AR, de Lara FM, Pendas AM, et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood. 2008;112(6):2539-2545.
20. Cooke KS, Hinkle B, Salimi-Moosavi H, et al. A fully human antihepcidin antibody modulates iron metabolism in both mice and nonhuman primates. Blood. 2013;122(17):3054-3061.