Antierythropoietin antibodies in thalassemia patients

Abstract

We evaluated sera from 58 thalassemic patients for the presence of antierythropoietin antibodies to investigate whether these autoantibodies may relate with modest response to treatment with recombinant human erythropoietin (rhEpo). Thirty-seven patients had beta-thalassemia major, 9 patients had beta-thalassemia intermedia, and 12 patients had sickle/beta(+)-thalassemia. Of 58 patients, 24 were on rhEpo treatment in order to increase the intervals between transfusions or the hemoglobin (Hb) values. The study population was divided into three groups according to rhEpo treatment. Group A consisted of 15 patients who were on rhEpo treatment (400-600 IU/kg three times per week, subcutaneously) showing an increase of Hb values or reduction of transfusion requirements. Group B included 9 patients who did not respond to rhEpo and group C consisted of 34 patients who did not receive rhEpo. Laboratory studies included a complete blood count, measurement of serum erythropoietin, immunological evaluation, and determination of antierythropoietin antibodies using enzyme-linked immunosorbent assay (ELISA). There were no significant differences among groups A, B, and C concerning age, Hb, and endogenous erythropoietin values. Fifteen patients had positive antinuclear antibodies and three patients had positive rheumatoid factor. Antierythropoietin antibodies were detected in the sera of seven patients (five men and two women) who received rhEpo. The male patients and one female patient had no response to rhEpo while the other female patient showed response when the dose increased. Other autoantibodies seem to have no clinical significance. In the present study, we detected for the first time in thalassemia patients the presence of antierythropoietin antibodies, which may contribute to rhEpo resistance. Thalassemia patients with low response rates to rhEpo should be evaluated for the presence of antierythropoietin antibodies.

Comparison of traditional methods and mitogen-stimulated direct antiglobulin test for detection of anti-red blood cell autoimmunity

“…In fact, cases which were positive only using MS-DAT, in which, unfortunately, eluates were not feasible as a first-step analysis, included patients suffering from B-CLL, myelodysplasia/aplasia, thalassemia intermedia, and hereditary spherocytosis (HS). Since mitogen stimulation induced autoantibody production and binding to autologous RBCs in culture, it is likely that MS-DAT is able to disclose latent anti-RBC autoimmunity in these diseases [11,22]. This could be of particular interest in B-CLL, where the negative prognostic significance of DAT positivity, even in the absence of AIHA, was demonstrated in a large prospective study [19].…”

Variant hemoglobin phenotypes may account for differential erythropoiesis-stimulating agent dosing in African-American hemodialysis patients

“…Finally, antibodies to erythropoietin may contribute to an impaired ESA response. Such antibodies have been reported in patients with β-thalassemia and sickle/β(+)-thalassemia, 18 but may not be common among ESRD patients. 19 Future studies should investigate the prevalence of such antibodies in ESRD patients in relation to their hemoglobin phenotype.…”

Sickle Trait in African-American Hemodialysis Patients and Higher Erythropoiesis-Stimulating Agent Dose

“…Our group previously reported that HbAS hemodialysis patients exhibit an increase in red cell phosphatidylserine exposure. 25 Antibodies to erythropoietin have been observed in individuals with hemoglobinopathies, 26 and although not specifically studied in ESRD patients with hemoglobinopathy traits, they could reduce the effect of erythropoietin and ESAs. Inflammation is a feature of overt sickle cell diseases, and in ESRD it contributes to ESA resistance by blunting iron use and erythropoiesis.…”