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Ethnicity-specific impact of HLA I/II genotypes on the risk of inhibitor development: data from Korean patients with severe hemophilia A

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Abstract

Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.

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Funding

This study was supported by a grant from the Korea Food & Drug Administration (KFDA) and by a grant from Korea Hemophilia Foundation.

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Author notes

  1. Hyun-Young Kim and Jin-Hee Cho contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Hyun-Young Kim, Jin-Hee Cho, Hee-Jung Kim, Hae-Sun Chung, Sun-Hee Kim & Hee-Jin Kim

  2. Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea

    Hyun-Young Kim

  3. Department of Laboratory Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, South Korea

    Hee-Jung Kim

  4. Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul, South Korea

    Hae-Sun Chung

  5. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea

    Ki-O Lee

  6. Korea Hemophilia Foundation, Seoul, South Korea

    Soo-Young Jung & Ki-Young Yoo

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  1. Hyun-Young Kim
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  2. Jin-Hee Cho
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  9. Hee-Jin Kim
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Corresponding authors

Correspondence to Ki-Young Yoo or Hee-Jin Kim.

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This study was approved by the Institutional Review Board of Samsung Medical Center (Seoul, Korea), and all patients gave written informed consent in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Kim, HY., Cho, JH., Kim, HJ. et al. Ethnicity-specific impact of HLA I/II genotypes on the risk of inhibitor development: data from Korean patients with severe hemophilia A. Ann Hematol 97, 1695–1700 (2018). https://doi.org/10.1007/s00277-018-3358-x

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  • DOI: https://doi.org/10.1007/s00277-018-3358-x

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