Case–Control Study of the Association Between Select
            <i>HLA</i>
            Genes and Anti-Erythropoietin Antibody-Positive Pure Red-Cell Aplasia

Fijal, Bonnie; Ricci, Deborah; Vercammen, Els; Palmer, Peter; Fotiou, Fotis; Fife, Daniel; Lindholm, Anders; Broderick, Erin; Francke, Stephan; Wu, Xiaodong; Colaianne, James; Cohen, Nadine

doi:10.2217/14622416.9.2.157

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…The human leukocyte antigen-A, -B, -DR, and -DQ genotypes of anti-r-HuEpo-positive cases will be typed to investigate the association of human leukocyte antigen-associated and anti-r-HuEpo-associated PRCA. The reason for determining this relationship was based on results obtained from recent studies 5,10 that showed the genetic susceptibility of human leukocyte antigen DR B1*09 to anti-r-HuEpo-associated PRCA in innovative r-HuEpo cases. It will be another 2 more years before we can analyze the data, but we are confident that the results of this registry study will enlighten us on how to deal with biosimilar r-HuEpo.…”

Section: Discussionmentioning

confidence: 99%

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Praditpornsilpa

Tiranathanagul

Kupatawintu

et al. 2011

Kidney International

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Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.

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Section: Discussionmentioning

confidence: 99%

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Praditpornsilpa

Tiranathanagul

Kupatawintu

et al. 2011

Kidney International

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“…40 Thai patients who were carriers of this allele were more likely to have developed PRCA than a control group consisting of kidney transplant candidates, 41 and a similar finding has been reported in Caucasian patients. 42 However, cases also developed in patients who were not carriers of this allele. This suggests that while this major histocompatibility complex allele may contribute to the susceptibility to developing anti-EPO antibodies, it is not an absolute requirement.…”

Section: Patient Characteristicsmentioning

confidence: 99%

Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights

Macdougall

Roger

Francisco

et al. 2012

Kidney International

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Antibody-mediated pure red cell aplasia is a very rare but devastating condition affecting patients receiving treatment with erythropoiesis-stimulating agents. New cases continue to emerge, generally in clusters, consistent with an 'environmental' trigger to its pathogenesis. Defining the causes of antibody-mediated pure red cell aplasia is clearly of importance for patients with chronic kidney disease, but any developments in this area may also have relevance to other disease areas as therapeutic delivery of endogenous proteins rapidly increases. This review focuses on the current knowledge regarding the etiology of antibody-mediated pure red cell aplasia and the current approach to therapy.

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“…This incidence is much higher than the incidence of anti-rHuEPO-induced PRCA in western countries 2 , 4 , 9 – 12 , 18 – 20 . Our previous data 4 and other groups 3 , 7 suggested the role of HLA-DRB1*09-DQB1*03:09 and HLA DRB1*12:02 as risk factors for anti-rHuEPO-induced PRCA. However, studies 3 , 4 , 7 were conducted in a small group of cases (24, 22, and 8 cases, respectively) using an intermediate resolution HLA genotyping technique; therefore, the exact relationships of all the genetic variability of HLA with anti-rHuEPO-induced PRCA cannot be fully determined.…”

Section: Introductionmentioning

confidence: 74%

HLA-B46:01:01:01 and HLA-DRB109:01:02:01 are associated with anti-rHuEPO-induced pure red cell aplasia

Suttichet,

Chamnanphon,

Pongpanich

et al. 2023

Sci Rep

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Treatment of anemia in patients with chronic kidney disease (CKD) with recombinant human erythropoietin (rHuEPO) can be disrupted by a severe complication, anti-rHuEPO-induced pure red cell aplasia (PRCA). Specific HLA genotypes may have played a role in the high incidence of PRCA in Thai patients (1.7/1,000 patient years vs. 0.03/10,000 patient years in Caucasians). We conducted a case–control study in 157 CKD patients with anti-rHuEPO-induced PRCA and 56 controls. The HLA typing was determined by sequencing using a highly accurate multiplex single-molecule, real-time, long-read sequencing platform. Four analytical models were deployed: Model 1 (additive: accounts for the number of alleles), Model 2 (dominant: accounts for only the presence or absence of alleles), Model 3 (adjusted additive with rHuEPO types) and Model 4 (adjusted dominant with rHuEPO types). HLA-B*46:01:01:01 and DRB1*09:01:02:01 were found to be independent risk markers for anti-rHuEPO-induced PRCA in all models [OR (95%CI), p-values for B*46:01:01:01: 4.58 (1.55–13.51), 0.006; 4.63 (1.56–13.75), 0.006; 5.72 (1.67–19.67), 0.006; and 5.81 (1.68–20.09), 0.005; for DRB1*09:01:02:01: 3.99 (1.28–12.49), 0.017, 4.50 (1.32–15.40), 0.016, 3.42 (1.09–10.74), 0.035, and 3.75 (1.08–13.07), 0.038, in Models 1–4, respectively. HLA-B*46:01:01:01 and DRB1*09:01:02:01 are susceptible alleles for anti-rHuEPO-induced PRCA. These findings support the role of HLA genotyping in helping to monitor patients receiving rHuEPO treatment.

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Case–Control Study of the Association Between Select HLA Genes and Anti-Erythropoietin Antibody-Positive Pure Red-Cell Aplasia

Abstract: This study confirmed that HLA-DRB19 occurs at a significantly higher frequency in Ab-positive PRCA cases than in controls; however, within this sample set, carrying the 9 allele was neither necessary nor sufficient to cause Ab-positive PRCA.

Cited by 11 publications

References 31 publications

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights

HLA-B46:01:01:01 and HLA-DRB109:01:02:01 are associated with anti-rHuEPO-induced pure red cell aplasia

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Case–Control Study of the Association Between Select HLA Genes and Anti-Erythropoietin Antibody-Positive Pure Red-Cell Aplasia

Abstract: This study confirmed that HLA-DRB1*9 occurs at a significantly higher frequency in Ab-positive PRCA cases than in controls; however, within this sample set, carrying the *9 allele was neither necessary nor sufficient to cause Ab-positive PRCA.

Cited by 11 publications

References 31 publications

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights

HLA-B*46:01:01:01 and HLA-DRB1*09:01:02:01 are associated with anti-rHuEPO-induced pure red cell aplasia

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Product

Resources

About

Abstract: This study confirmed that HLA-DRB19 occurs at a significantly higher frequency in Ab-positive PRCA cases than in controls; however, within this sample set, carrying the 9 allele was neither necessary nor sufficient to cause Ab-positive PRCA.

HLA-B46:01:01:01 and HLA-DRB109:01:02:01 are associated with anti-rHuEPO-induced pure red cell aplasia