Annals of Hematology

, Volume 65, Issue 6, pp 265–268 | Cite as

Iron stores and serum transferrin receptor levels during recombinant human erythropoietin treatment of anemia in rheumatoid arthritis

  • G. Vreugdenhil
  • B. Manger
  • C. Nieuwenhuizen
  • R. A. Feelders
  • H. G. van Eijk
  • A. J. G. Swaak
Original Article


Ten rheumatoid arthritis (RA) patients with anemia of chronic disorders (ACD) were treated with recombinant human erythropoietin (r-Hu-Epo) using a dose of 250 U/kg s.c. 3 times a week for 6 weeks, in order to evaluate its effects on the anemia, iron stores, and serum-soluble transferrin receptor (sTfR) levels. All patients showed a rise in hemoglobin (Hb). Median Hb increased from 5.9 (5.5–7.0) at baseline to 6.7 (5.8–7.8) at 3 weeks and to 7.2 (5.9–8.5) mmol/l at 6 weeks during treatment. Ferritin levels decreased significantly during the 6 weeks, and five patients were iron deficient after 6 weeks of treatment. TfR levels increased significantly at 3 and 6 weeks during treatment.

These preliminary findings may indicate that r-Hu-Epo is effective in improving ACD in RA. The sTfR rise may be explained by an increase in erythroid precursor cell mass or increased TfR expression and a decrease in tissue iron stores, although direct effects of Epo on TfR regulation cannot be excluded. Large double-blind studies with r-Hu-Epo in patients with RA and ACD are warranted.

Key words

Erythropoietin Recombinant human ery thropoietin Anemia Rheumatoid arthritis Iron stores Transferrin receptor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baer AN, Dessypriss EN, Goldwasser E, Krantz S (1987) Blunted erythropoietin response to anaemia in rheumatoid arthritis. Br J Haematol 66: 559–564PubMedGoogle Scholar
  2. 2.
    Baynes RD, Shih YJ, Cook JD (1991) Production of soluble transferrin receptor by K562 erythroleukemia cells. Br J Haematol 78: 450–455PubMedGoogle Scholar
  3. 3.
    Beguin Y, Lipscei G, Thoumsin H, Fillet G (1991) Blunted erythropoietin production and decreased erythropoiesis in early pregnancy. Blood 78: 89–93PubMedGoogle Scholar
  4. 4.
    Birgegard G, Hallgren R, Caro J (1987) Serum erythropoietin in rheumatoid arthritis and other inflammatory arthritides. Relationship to anaemia and the effect of anti-inflammatory treatment. Br J Haematol 65: 479–483PubMedGoogle Scholar
  5. 5.
    Boyd HK, Lappin TRJ (1991) Erythropoietin deficiency in the anaemia of chronic disorders. Eur J Haematol 46: 198–201PubMedGoogle Scholar
  6. 6.
    Cazzola M, Beguin Y, Ponchio L, et al. (1991) Serum erythropoietin and transferrin receptor as clinical tools for predicting and evaluating erythroid marrow response to recombinant human erythropoietin (rHuEPO). Blood 78 [Suppl 1]: 90 a (abstract)Google Scholar
  7. 7.
    Eckardt KU, Kurtz A, Hirth P, Shicalla P, Wieczorek L, Bauer C (1988) Quantitative determination of erythropoietin (Epo) in serum by radioimmunoassay. Klin Wochenschr 66: 241–245PubMedGoogle Scholar
  8. 8.
    Eschbach JW, Egrie JC, Downing MR, et al. (1987) Correction of the anemia of end-stage renal disease with recombinant human erythropoietin: results of a phase-I und -II clinical trial. N Engl J Med 316: 73–78PubMedGoogle Scholar
  9. 9.
    Fischl M, Galpin JE, Levin JD, et al. (1990) Recombinant human erythropoietin for patients with AIDS treated with zidovudine. N Engl J Med 332: 1488–1493Google Scholar
  10. 10.
    Flowers CH, Skikne BS, Covell AM, Cook JD (1989) The clinical measurement of serum transferrin receptor. J Lab Clin Med 114: 368–377PubMedGoogle Scholar
  11. 11.
    Huebers HA, Beguin Y, Pootrakul P, Einspahr D, Finch CA (1990) Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood 75: 102–107PubMedGoogle Scholar
  12. 12.
    Kohgo Y, Nishisato T, Kondo H, Tsushima N, Niitsu Y, Urushshizaki I (1986) Circulating transferrin receptor in human serum. Br J Haematol 64: 277–281PubMedGoogle Scholar
  13. 13.
    Kohgo Y, Niitsu Y, Kato J, et al. (1987) Serum transferrin receptor as a new index of erythropoiesis. Blood 70: 1955–1958PubMedGoogle Scholar
  14. 14.
    Krantz SB (1991) Erythropoietin. Blood 77: 419–434PubMedGoogle Scholar
  15. 15.
    Ludwig H, Fritz E, Katzmann H, et al. (1990) Erythropoietin treatment of anemia associated with multiple myeloma. N Engl J Med 322: 1693–1699PubMedGoogle Scholar
  16. 16.
    Manger B, Weiss A, Hardy KJ, Stobo JD (1986) A transferrin receptor antibody represents one signal for the induction of IL2 production by a human T-cell line. J Immunol 136: 532–538PubMedGoogle Scholar
  17. 17.
    Manger B, Nusslein I, Woith W, Winkler T, Herrmann M, Kalden JR (1991) Release of soluble transferrin receptor (TfR) by activated human lymphocytes. Immunobiology 183: 350 (Abstract)Google Scholar
  18. 18.
    Pincus T, Olsen NJ, Russell IJ, et al. (1990) Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. Am J Med 89: 161–168PubMedGoogle Scholar
  19. 19.
    Sawyer ST, Krantz SB (1988) Transferrin receptor number, synthesis and endocytosis during erythropoietin-induced maturation of Friend virus-infected erythroid cells. J Biol Chem 261: 9187–9195Google Scholar
  20. 20.
    Skikne BS, Flowers C, Cook JD (1990) Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 75: 1870–1876PubMedGoogle Scholar
  21. 21.
    Takashina N, Kondo H, Kashiwazaki S (1990) Suppressed serum erythropoietin response to anemia and the efficacy of recombinant erythropoietin in the anemia of rheumatoid arthritis. J Rheumatol 17: 885–887PubMedGoogle Scholar
  22. 22.
    Vreugdenhil G, Swaak AJG (1990) Review. Anaemia in rheumatoid arthritis: pathogenesis, diagnosis and treatment. Rheumatol Int 9: 243–257PubMedGoogle Scholar
  23. 23.
    Vreugdenhil G, Swaak AJG (1990) Review. The role of erythro-poietin in the anaemia of chronic disease in rheumatoid arthritis. Clin Rheumatol 9: 22–27PubMedGoogle Scholar
  24. 24.
    Vreugdenhil G, Baltus JAM, Van Eijk HG, Swaak AJG (1990) Anaemia of chronic disease: diagnostic significance of erythrocyte and serological parameters in iron-deficient rheumatoid arthritis patients. Br J Rheumatol 29: 105–110PubMedGoogle Scholar
  25. 25.
    Vreugdenhil G, Kroos MJ, Van Eijk HG, Lowenberg B, Swaak AJG (1990) Impaired iron uptake and transferrin binding by erythroblasts in anaemia in rheumatoid arthritis. Br J Rheumatol 29: 335–339PubMedGoogle Scholar
  26. 26.
    Vreugdenhil G, Wognum AW, Van Eijk HG, Swaak AJG (1990) Anaemia in rheumatoid arthritis. The role of iron, vitamin B12 and folic acid deficiency and erythropoietin responsiveness. Ann Rheum Dis 49: 93–98PubMedGoogle Scholar
  27. 27.
    Weinfeld A (1964) Storage iron in man. Acta Med Scand 11 [Suppl 1]: 427–429Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • G. Vreugdenhil
    • 1
  • B. Manger
    • 2
  • C. Nieuwenhuizen
    • 3
  • R. A. Feelders
    • 4
  • H. G. van Eijk
    • 4
  • A. J. G. Swaak
    • 3
  1. 1.Department Internal Medicine, Division of HematologyUniversity Hospital NijmegenHB NijmegenThe Netherlands
  2. 2.Institute of Clinical Immunology and Rheumatology Department Medicine IIIMedical School ErlangenFederal Republic of German
  3. 3.Department RheumatologyDr. Daniel Den Hoed ClinicRotterdamThe Netherlands
  4. 4.Department Chemical Pathology, Medical FacultyErasmus UniversityRotterdamThe Netherlands

Personalised recommendations