Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor.
We report a case of anemia due to autoantibodies to the transferrin receptor interfering with iron incorporation by erythroid progenitors. A previously healthy woman with severe acquired microcytic anemia had increased serum iron levels, electrophoretically normal transferrin concentrations, and very high levels of free protoporphyrin in red cells. The bone marrow had no stainable iron but had an excess of normal-appearing plasma cells. Erythroid precursors stained with fluorescent mouse antihuman IgM. The serum contained an antibody that reduced 59Fe incorporation by erythroleukemia K562 cells in vitro but did not inhibit iron transferrin binding. An IgM fraction of the patient's serum immunoprecipitated the human transferrin receptor obtained from solubilized [35S]methionine-labeled K562 membranes. Binding of [59Fe]transferrin or fluorescent iron transferrin was not diminished by the patient's serum at 4 degrees C, but at 37 degrees C uptake was markedly reduced, as was the binding of fluorescent monoclonal antibodies to either surface transferrin or the human transferrin receptor. A complete clinical and hematologic remission occurred with azathioprine and prednisone therapy. We conclude that the patient's autoreactive IgM down-regulated the number of transferrin receptors and diminished iron incorporation by erythroblasts, leading to an iron-deficiency anemia.
D000747:Anemia, Hypochromic / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D001379:Azathioprine / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007504:Iron Radioisotopes; D011241:Prednisone / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007075:Immunoglobulin M; D007504:Iron Radioisotopes; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron; D001379:Azathioprine; D011241:Prednisone