HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity
oleh: 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
| Format: | Article |
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| Diterbitkan: | Elsevier 2024-05-01 |
Deskripsi
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.