Fine epitope specificity of anti-erythropoietin antibodies reveals molecular mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related anemia.
J Infect Dis
; 204(6): 902-11, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21849287
ABSTRACT
BACKGROUND:
Circulating autoantibodies to endogenous erythropoietin (anti-Epo) are detected in human immunodeficiency virus type 1 (HIV-1)-infected patients and represent a risk factor for anemia. The aim of this study was to map the B-cell epitopes on the Epo molecule.METHODS:
Serum samples from HIV-1-positive patients and healthy individuals were tested against overlapping peptides covering the entire sequence of Epo.RESULTS:
Serum samples from anti-Epo-positive patients exhibited significant binding to Epo epitopes spanning the following sequences amino acids 1-20 (Ep1), amino acids 54-72 (Ep5), and amino acids 147-166 (Ep12). Structural analysis of erythropoietin revealed that the immunodominant epitopes, Ep1 and Ep12, comprise the interaction interface with Epo receptor (EpoR). Autoantibodies binding to this specific region are anticipated to inhibit the Epo-EpoR interaction, resulting in blunted erythropoiesis; this phenomenon is indicated by the significantly higher Epo levels and lower hemoglobin levels of anti-Ep1-positive patients compared with anti-Ep1-negative individuals. The region corresponding to the Ep1 epitope exhibited a 63% sequence homology with the ³4LVCASRELERFAVNPGLLE5² fragment of the HIV-1 p17 matrix protein.CONCLUSIONS:
These results suggest that the main body of anti-Epo is directed against a functional domain of Epo, and that the presence of anti-Epo can be considered to be a result of a molecular mimicry mechanism, which is caused by the similarity between the Ep1 region and the p17 protein.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos HIV
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Infecções por HIV
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Eritropoetina
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HIV-1
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Mimetismo Molecular
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Epitopos de Linfócito B
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Produtos do Gene gag do Vírus da Imunodeficiência Humana
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Anemia
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article