title: Autoantibodies to erythropoietin receptor in patients with immune-mediated diseases: relationship to anaemia with erythroid hypoplasia.
abstract: 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.
authors.affiliation: Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hara
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Masato
authors.initials: M
authors.lastname: Higuchi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.forename: Norihiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line / Q000187:drug effects; D002648:Child; D002908:Chronic Disease; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000276:immunology / Q000473:pathology; D004920:Erythropoiesis / Q000276:immunology*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007674:Kidney Diseases / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017467:Receptors, Erythropoietin / Q000276:immunology*; D017701:Reticulocyte Count; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006454:Hemoglobins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017467:Receptors, Erythropoietin