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]
日期:2008-01-29
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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