Association of HLA genotypes with Beta-lactam antibiotic hypersensitivity in children

Prapasiri Singvijarn,¹ Wiparat Manuyakorn,¹ Surakameth Mahasirimongkol,² Sukanya Wattanapokayakit,² Wimala Inunchot,² Nuanjun Wichukchinda,² Supharat Suvichapanich,³ Wasu Kamchaisatian,¹ Suwat Benjaponpitak¹

¹ Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
² Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
³ Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

Abstract

Background: Beta-lactam (BL) antibiotics hypersensitivity is common in children. Clinical manifestation of BL hypersensitivity varies from mild to severe cutaneous adverse drug reactions (SCARs).
Objective: To determine the association of HLA genotype and BL hypersensitivity and the prevalence of true drug allergy in patients with history of BL hypersensitivity.
Methods: A case-control study was performed in 117 children with aged 1-18 years. Children with history of non-SCARs BL hypersensitivity were evaluated for true drug hypersensitivity including skin test and drug provocation test. Tolerant control patients were children who could tolerate BL for at least 7 days without hypersensitivity reaction. HLA genotype (HLA-A, HLA-B, HLA-C and HLA-DRB1) were performed in 24 cases and 93 tolerant controls using PCR-SSO (polymerase chain reaction – sequence specific oligonucleotide probes).
Results: There were association of HLA-C04:06 (OR = 13.14, 95%CI: 1.3-137.71; p = 0.027), and HLA-C08:01 (OR = 4.83, 95%CI: 1.93-16.70; p = 0.016) with BL hypersensitivity. HLA-B48:01 was strongly associated with immediate reaction from BL hypersensitivity (OR = 37.4, 95%CI: 1.69-824.59; p = 0.016) while HLA-C04:06, HLA-C08:01 and HLA-DRB104:06 were associated with delayed reaction (p < 0.05). Among 71 cases who were newly evaluated for BL hypersensitivity, only 7 cases (9.8%) had true BL hypersensitivity.
Conclusions: Less than 10% of children with suspected of BL hypersensitivity have true hypersensitivity. There might be a role of HLA-B, HLA-C and HLA-DRB1 genotype in predicting BL hypersensitivity in Thai children.
Key words: HLA-B48:01, HLA-C04:06, HLA-C08:01, HLA-DRB104:06, Drug reaction, Thai,