Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin.
BACKGROUND
Within a period of three years, we identified 13 patients in whom pure red-cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We investigated whether there was an immunologic basis for the anemia in these patients.


METHODS
Serum samples from the 13 patients with pure red-cell aplasia were tested for neutralizing antibodies that could inhibit erythroid-colony formation by normal bone marrow cells in vitro. The presence of antierythropoietin antibodies was identified by means of binding assays with the use of radiolabeled intact, deglycosylated, or denatured epoetin.


RESULTS
Serum from all 13 patients blocked the formation of erythroid colonies by normal bone marrow cells. The inhibition was reversed by epoetin. Antibodies from 12 of the 13 patients bound only conformational epitopes in the protein moiety of epoetin; serum from the remaining patient bound to both conformational and linear epitopes in erythropoietin. In all the patients, the antibody titer slowly decreased after the discontinuation of treatment with epoetin.


CONCLUSIONS
Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin.
Casadevall
Nicole
N
Department of Hematology, Hotel-Dieu, Paris, France. nicole.casadevall@htd.ap-hop-paris.fr
Nataf
Joelle
J
Viron
Beatrice
B
Kolta
Amir
A
Kiladjian
Jean-Jacques
JJ
Martin-Dupont
Philippe
P
Michaud
Patrick
P
Papo
Thomas
T
Ugo
Valerie
V
Teyssandier
Irene
I
Varet
Bruno
B
Mayeux
Patrick
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division; D000068817:Epoetin Alfa; D015672:Erythroid Precursor Cells / Q000166:cytology; D004921:Erythropoietin / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D008875:Middle Aged; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000097:blood / Q000139:chemically induced* / Q000276:immunology
D001323:Autoantibodies; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068817:Epoetin Alfa