Τίτλος:
Fine epitope specificity of anti-erythropoietin antibo reveals molecular mimicry with HIV-1 p17 protein: A pathogenetic mechanism for HIV-1-relate anemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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: OMethylN(3DeoxyLGlyceroTetronyl)DPerosamine (4Amino 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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Συγγραφείς:
Tsiakalos, A.
Routsias, J.G.
Kordossis, T.
Moutsopoulos, H.M.
Tzioufas, A.G.
Sipsas, N.V.
Περιοδικό:
JOURNAL OF INFECTIOUS DISEASES
Λέξεις-κλειδιά:
epitope; erythropoietin; erythropoietin antibody; erythropoietin receptor; hemoglobin; protein p17, adult; amino acid sequence; anemia; antibody specificity; antigen binding; antigen detection; article; blood sampling; clinical article; controlled study; dyserythropoiesis; epitope mapping; female; hemoglobin blood level; human; Human immunodeficiency virus 1 infection; male; molecular mimicry; pathogenesis; priority journal; protein binding; protein blood level; protein protein interaction; protein structure; receptor binding; sequence homology; structure analysis, Adult; Anemia; Epitope Mapping; Epitopes, B-Lymphocyte; Erythropoietin; Female; gag Gene Products, Human Immunodeficiency Virus; HIV Antigens; HIV Infections; HIV-1; Humans; Male; Middle Aged; Molecular Mimicry
DOI:
10.1093/infdis/jir433
