Case–control study of the association between select HLA genes and anti-erythropoietin antibody-positive pure red-cell aplasia

纯红细胞再生障碍 促红细胞生成素 抗体 人类白细胞抗原 基因 再生障碍 免疫学 医学 生物 遗传学 内科学 抗原 贫血
作者
Bonnie A. Fijal,Deborah Ricci,Els Vercammen,Peter Palmer,Fotis Fotiou,Daniel Fife,Anders Lindholm,Erin Broderick,Stephan Francke,Xiaodong Wu,James Colaianne,Nadine Cohen
出处
期刊:Pharmacogenomics [Future Medicine]
卷期号:9 (2): 157-167 被引量:12
标识
DOI:10.2217/14622416.9.2.157
摘要

Aims: Antibody (Ab)-positive pure red-cell aplasia (PRCA) is a very rare but serious adverse event associated with recombinant human erythropoietin treatment (4.1 reports per 100,000 patient-years) in which patients produce antibodies to recombinant and endogenous erythropoietin, halting red blood cell production. In a previous case series, four Thai subjects with chronic kidney disease and Ab-positive PRCA were reported to have the HLA-DRB1*9 allele. To confirm a possible association of HLA-DRB1*9 and Ab-positive PRCA, we performed a pharmacogenomic analysis using subjects from an earlier case–control study of risk factors associated with Ab-positive PRCA, which had been performed using subjects from Europe or Canada. The primary goal of the analysis was to test the association between HLA-DRB1*9 and Ab-positive PRCA. A secondary goal was to perform an exploratory analysis in order to identify additional HLA alleles potentially associated with Ab-positive PRCA. Patients & Methods: Subjects were taken from a case–control study of Ab-positive PRCA in chronic kidney disease patients treated in Europe or Canada. Ab-positive PRCA cases (n = 24) were matched to controls (n = 81) by timing of treatment exposure and, when possible, by location. Results: The allele frequency of HLA-DRB1*9 was 12.5% in cases vs 1.2% in controls (p = 0.002). The frequency of the HLA-DRB1*9/other genotype was 25.0% in cases vs 2.5% in controls (p = 0.004; OR: 10.8 [95% CI: 2.2–53.7]). Within the exploratory analysis, six additional HLA alleles (HLA-A*25, HLA-B*53, HLA-C*12, HLA-DQB1*3, HLA-DQB1*6 and HLA-DRB1*4) were also found to be associated with Ab-positive PRCA. Conclusion: 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.
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