![]() The development of autoantibodies against endogenous EPO in patients who have never been treated with ESAs is very rare 14. ![]() The anti-rHuEPO neutralizing antibodies cross-react with endogenous EPO. Most of these reported cases were in patients receiving rHuEPO for the treatment of CKD-related anemia. Several reports have shown that the number of reported cases with PRCA due to the development of neutralizing antibodies against endogenous EPO and recombinant erythropoiesis-stimulating agents (ESAs) has increased worldwide 7, 8, 9, 10, 11, 12, 13. Indeed, treatment of anemia with rHuEPO has been shown to improve the quality of life (QoL) of these patients 5, 6. rHuEPO has also been used to accelerate erythropoiesis in surgery, post-chemotherapy and post-transplantation 4. These include patients having chronic kidney disease (CKD), patients dependent on dialysis, HIV infection and malignancy. Recombinant human erythropoietin (rHuEPO) is administered to patients who have lower hemoglobin levels because of their inability to produce enough endogenous erythropoietin. Post-translational modification of this protein results in the addition of 4 carbohydrate chains: 3 N-linked and 1 O-linked glycosylation 1, 2, 3, following which the molecular weight of erythropoietin is roughly 40% increased from its original mass. EPO contains 165 amino acids, which contributes to the relative molecular mass of around 30,600 daltons. These engineered proteins could be the potential candidates to treat patients who are rHuEpo-dependent and express the HLA-DRB1*09 allele.Įrythropoietin (EPO) is a protein hormone produced by the kidneys and plays an essential role in the production and maturation of red blood cells (RBCs), which carry oxygen from the lungs to the rest of the body. Five out of seventeen mutants were less immunogenic in vitro while retaining similar or slightly reduced bioactivity than rHuEPO. In this study, we used computational design to screen for immunogenic hotspots recognized by HLA-DRB1*09, and predicted seventeen mutants having anywhere between one through four mutations that reduce affinity for the allele, without disrupting the structural integrity and bioactivity. Previous studies have reported an association between the development of anti-rHuEpo-associated PRCA and the HLA-DRB1*09 gene, which is reported to be entrenched in the Thai population. ![]() The immunogenic antibody response activated by rHuEPO is believed to be triggered by T-cells recognizing EPO epitopes bound to MHC molecules displayed on the cell surface of APCs. However, some patients repeatedly receiving rHuEPO develop anti-rHuEPO neutralizing antibodies leading to the development of pure red cell aplasia (PRCA). Recombinant human erythropoietin (rHuEPO) is a biopharmaceutical drug given to patients who have a low hemoglobin related to chronic kidney disease, cancer or anemia.
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