An in vivo model to assess factors that may stimulate the generation of an immune reaction to erythropoietin.
Int Immunopharmacol
; 6(4): 647-55, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16504928
ABSTRACT
The incidence of pure red cell aplasia (PRCA) in patients with chronic kidney disease associated with the subcutaneous (s.c.) administration of epoetin alfa (EPREX) began to increase in 1998. As part of an intensive investigation into the reasons for this increase, in vivo models were developed to assess the ability of potential causative factors to stimulate an immune response to recombinant human erythropoietin (rHuEPO). It was difficult to generate anti-EPO antibodies in mice. In animals injected with rHuEPO alone, anti-EPO antibodies were either absent or present at very low levels. The addition of an adjuvant to the immunization protocol was able to increase both the frequency of occurrence and titer of the immune response and resulted in the generation of anti-EPO antibodies that, in most cases, recognized both human and mouse EPO. Some mice exhibited a reduction in hematocrit, suggesting neutralization of endogenous EPO by anti-EPO antibodies. To evaluate the primary lead identified in the technical investigation, leachates from the uncoated syringe stoppers of EPREX syringes, a surrogate antigen (chicken egg albumin, OVA) was used to avoid possible interferences that could arise from the use of an endogenous protein like EPO. These leachates yielded a positive, concentration-dependent antibody response in the OVA animal model, demonstrating their adjuvant properties and providing support for the hypothesis generated through the technical investigation that leachates were capable of enhancing the immune response to rHuEPO.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Eritropoetina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Int Immunopharmacol
Ano de publicação:
2006
Tipo de documento:
Article