HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity

So-Young Park; So Young Park; Sujin Seo; Hyouk-Soo Kwon; Seung-Hyun Kim; Sae-Hoon Kim; Hye-Kyung Park; Yoon-Seok Chang; Cheol-Woo Kim; Byung Jae Lee; Hae-Sim Park; You Sook Cho; Heung-Bum Oh; David A Ostrov; Sungho Won; Tae Bum Kim

doi:10.1016/j.waojou.2024.100901

HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity

World Allergy Organ J. 2024 Apr 13;17(5):100901. doi: 10.1016/j.waojou.2024.100901. eCollection 2024 May.

Authors

So-Young Park^{1

2

3}, So Young Park¹, Sujin Seo⁴, Hyouk-Soo Kwon¹, Seung-Hyun Kim⁵, Sae-Hoon Kim⁶, Hye-Kyung Park⁷, Yoon-Seok Chang⁶, Cheol-Woo Kim⁸, Byung Jae Lee⁹, Hae-Sim Park⁵, You Sook Cho¹, Heung-Bum Oh¹⁰, David A Ostrov¹¹, Sungho Won⁴, Tae Bum Kim¹

Affiliations

¹ Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
² Division of Pulmonary, Allergy and Critical Care Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea.
³ Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
⁴ Department of Public Health Science, Seoul National University, Seoul, South Korea.
⁵ Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
⁶ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
⁷ Department of Internal Medicine, School of Medicine, Busan National University, Busan, South Korea.
⁸ Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea.
⁹ Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
¹⁰ Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
¹¹ Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, USA.

Abstract

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity.

Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site.

Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10^-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002).

Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.

Keywords: Cefaclor; Cephalosporin; Drug hypersensitivity; Immediate hypersensitivity; Whole exome sequencing.