title: Fine epitope specificity of anti-erythropoietin antibodies reveals molecular mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related anemia.
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.
authors.affiliation: Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece. atsiakalos@gmail.com
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Tsiakalos
authors.forename: John G
authors.initials: JG
authors.lastname: Routsias
authors.forename: Theodore
authors.initials: T
authors.lastname: Kordossis
authors.forename: Haralampos M
authors.initials: HM
authors.lastname: Moutsopoulos
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Tzioufas
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Sipsas
mesh_terms: D000328:Adult; D000740:Anemia / Q000209:etiology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D004921:Erythropoietin / Q000276:immunology*; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: C554270:EPO protein, human; D018985:Epitopes, B-Lymphocyte; D015488:HIV Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D004921:Erythropoietin