Biology Reference
In-Depth Information
with Eprex modifications could possibly lead to the production of the anti-
bodies. Lines of investigation such as linkage with a specific HLA subtype
having been eliminated,and we must consider more subtle parameters such as
possible polymorphisms of the EPO molecule itself. Theoretically, these poly-
morphisms could affect either the proteinic part of the EPO molecule itself
(direct polymorphism of the
EPO
gene) or the glycohydrates of the EPO mol-
ecule (differences in the glycosylation process). The later, however, seems
unlikely because antibodies are directed against the protein moiety of the mol-
ecule and because, as previously stated, Eprex seems to be more similar to
endogenous EPO than NeoRecormon in terms of glycosylation. Clearly, the
possible polymorphisms should be carefully examined since, if present, they
could permit identification of a population that should not receive rHuEPO
treatment.
rHuEPO is also used to correct anemia associated to other pathologies such
as cancer, hematologic malignancy, or auto-immunodeficiency syndrome
(AIDS), as well as for illegal blood doping in many sports. No anti-EPO anti-
bodies have been detected to date in any patient or athlete treated with
rHuEPO. A study on a limited number of patients with myelodysplatic syn-
dromes, some treated and some not with rHuEPO, did not detect anti-EPO
antibodies even in those with a low response to rHuEPO [20]. Two reasons
could explain why these patients did not develop antibodies. First, in patients
with cancer, hematologic malignancy, or AIDS, we can hypothesize that they
have overall decreased immune responses with lower probability of develop-
ing antibodies. Moreover, these patients are usually treated for shorter periods
with rHuEPO than are patients with chronic renal failure. The lack of a case of
anti-EPO antibodies in athletes illegally using rHuEPO for blood doping is
more of a problem of numbers of abusers, since the incidence of antibodies is
low in the larger population of patients treated with rHuEPO. Nevertheless, the
degree and duration of the anemia observed in patients developing antibodies,
leading to long-lasting red blood cell transfusion, enforce the ban against the
use of rHuEPO outside recognized medical indications.
When should a physician ask for an anti-EPO antibody test? Systematically
testing all patients treated with rHuEPO is clearly unnecessary. Indeed,the
sensitivity of the currently available tests is such that the patients should pres-
ent objective symptoms before antibodies could be detected. The low percent-
age of patients developing anti-EPO antibodies would make this screening
very expensive for a poor result, and except for the immediate halt to rHuEPO
treatment, no clear therapy could be proposed to rapidly ameliorate antibody
formation. Such testing, however, should be done rapidly in case of a sudden
appearance of an aregenerative anemia without other classical cases of anemia
(viral infection, bleeding, inflammation, iron deficiency). Moreover, antibody
titer must be steadily determined to follow the efficiency of immunosuppres-
sive treatment.
