Biology Reference
In-Depth Information
Antibodies to endogenous and recombinant
erythropoietin
Patrick Mayeux
1
and Nicole Casadevall
2
1
Institut Cochin, Département d'Hématologie, INSERM U567, Université René Descartes, Hôpital
Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
2
Hôpital de l'Hôtel-Dieu, Service d'Hématologie Biologique, INSERM U362, 1, Place du Parvis
Notre Dame, 75181 Paris cedex 4, France
Introduction
Owing to the very few cases of anti-erythropoietin (EPO) antibodies arising in
patients treated with recombinant human EPO (rHuEPO) before 1998, it was
generally believed that EPO is weakly immunogenic. Several recent reports,
however, suggest that this theory may be wrong. Indeed, low amounts of
rHuEPO are immunogenic in animals such as the mouse, rat, rabbit, or horse,
despite the high degree of sequence identity of the mammalian EPO mole-
cules. Interestingly, in most cases injection of rHuEPO to these animals not
only leads to production of antibodies that recognize the injected rHuEPO but
also cross react with the endogenous EPO molecule and neutralize it, leading
to pronounced anemia in rHuEPO-treated animals [1, and our own unpub-
lished data]. A hybrid molecule linking recombinant human granulocyte-
macrophage colony-stimulating factor (rHuGM-CSF) and EPO has been
administrated to rhesus monkeys. This treatment induced a neutralizing
immune response to EPO, whereas no antibodies against GM-CSF were
detected. Again, the anti-EPO antibodies cross reacted with monkey EPO and
induced a pronounced anemia [2]. Thus, the low incidence of neutralizing anti-
EPO antibodies among rHuEPO-treated patients is most likely due to the good
quality of the available rHuEPO preparations rather than to a low antigenic
property of the molecule itself. rHuEPO appears to differ from endogenous
human EPO only at the level of glycosylation. This high similarity explains
why rHuEPO treatment exhibits a high degree of both efficiency and safety.
During the last four years, however, a large number of cases of pure red cell
aplasia due to neutralizing anti-EPO antibodies have been reported in patients
treated with rHuEPO for anemia associated with renal failure of various eti-
ologies [3]. In this review, we address several questions:
• What is the incidence of anti-EPO antibodies?
•What are the characteristics of these antibodies?
