Autoantibodies to erythropoietin receptor in patients with immune-mediated diseases: relationship to anaemia with erythroid hypoplasia

Authors

  • Akinori Hara,

    1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
    2. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Kengo Furuichi,

    1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
    2. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Masato Higuchi,

    1. Medical Research Institute, Kanazawa Medical University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Yasunori Iwata,

    1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
    2. Department of Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Norihiko Sakai,

    1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
    2. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Shuichi Kaneko,

    1. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    Search for more papers by this author
  • Takashi Wada

    Corresponding author
    1. Department of Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
    • Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
    Search for more papers by this author

Correspondence: Takashi Wada, Division of Nephrology, Kanazawa University , Hospital, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

E-mail: twada@m-kanazawa.jp

Summary

The prevalence, clinical associations and pathogenic role of newly identified autoantibodies to the erythropoietin receptor (EPOR) in patients with anaemia were investigated. Sera from 203 patients with immune-related or chronic kidney diseases were screened for anti-EPOR antibodies by enzyme-linked immunosorbent assay, and antibody specificity was evaluated by immunoprecipitating EPOR from AS-E2 cells using purified immunoglobulin (Ig) fractions. In addition, the pathogenic role of anti-EPOR antibodies was determined by examining their inhibitory effects on AS-E2 cell proliferation. Clinical findings were compared between patients with and without anti-EPOR antibodies, in all patients and those with systemic lupus erythematosus (SLE). Serum anti-EPOR antibodies were detected in 52 patients. Purified IgG or IgM fractions from anti-EPOR antibody-positive sera immunoprecipitated EPOR and inhibited the EPO-dependent proliferation of AS-E2 cells in a dose-dependent manner. Anti-EPOR antibodies were associated with low haemoglobin concentrations and reticulocytopenia in all patients enrolled and those with SLE. Further, there was a negative correlation between the levels of anti-EPOR antibodies and the number of bone marrow erythroblasts in patients who underwent bone marrow examinations. These findings suggest that EPOR autoantibodies are present in a subset of patients with anaemia and that impaired erythropoiesis can be mediated by anti-EPOR antibodies, which functionally neutralize EPO activity.

Ancillary