HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity

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

World Allergy Organization Journal (May 2024)

HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity

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

Affiliations

So-Young Park, MD, PhD: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Division of Pulmonary, Allergy and Critical Care Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, South Korea; Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea
So Young Park, MD, PhD: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Sujin Seo, BS: Department of Public Health Science, Seoul National University, Seoul, South Korea
Hyouk-Soo Kwon, MD, PhD: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Seung-Hyun Kim, PhD: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea
Sae-Hoon Kim, MD, PhD: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
Hye-Kyung Park, MD, PhD: Department of Internal Medicine, School of Medicine, Busan National University, Busan, South Korea
Yoon-Seok Chang, MD, PhD: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
Cheol-Woo Kim, MD, PhD: Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
Byung Jae Lee, MD, PhD: Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Hae-Sim Park, MD, PhD: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea
You Sook Cho, MD, PhD: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Heung-Bum Oh, PhD: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
David A. Ostrov, PhD: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, USA
Sungho Won, PhD: Department of Public Health Science, Seoul National University, Seoul, South Korea; Corresponding author. Department of Public Health Science, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea.
Tae Bum Kim, MD, PhD: Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Corresponding author. Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, 138-736, South Korea.

Journal volume & issue: Vol. 17, no. 5
p. 100901

Abstract

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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.

Published in World Allergy Organization Journal

ISSN: 1939-4551 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: https://www.journals.elsevier.com/world-allergy-organization-journal/

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