Journal
BLOOD
Volume 116, Issue 22, Pages 4542-4545Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-04-280875
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- Proteus
- CEA
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Antibody-mediated pure red cell aplasia is a rare but serious event resulting from the induction of neutralizing erythropoietin (Epo)-specific antibodies provoked by treatment with recombinant Epo. Because of the crucial role of CD4 T cells in humoral response, we have quantified the number of Epo-specific CD4 T cells in the blood of normal donors by in vitro stimulation. An important repertoire of preexisting Epo-specific T cells was observed in almost half of the donors, comparable with that of non-self-proteins. This observation suggests that, at the steady state, endogenous Epo weakly contributes to tolerance induction and may be ignored by the immune system. As a result, circulating Epo-specific CD4 T cells could be prone to be activated by altered batches of Epo, providing them with costimulatory signals. Our data also highlight the relevance of T-cell assays performed with normal donors to evaluate the potential immunogenicity of therapeutic proteins. (Blood. 2010; 116(22): 4542-4545)
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