PMID- 37795024
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231030
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Association between HLA alleles and beta-lactam antibiotics-related severe 
      cutaneous adverse reactions.
PG  - 1248386
LID - 10.3389/fphar.2023.1248386 [doi]
LID - 1248386
AB  - Introduction: Beta-lactam antibiotics are one of the most common causes of 
      antibiotics-related severe cutaneous adverse reactions (SCARs) including 
      Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reactions 
      with eosinophilia and systemic symptoms (DRESS), and acute generalized 
      exanthematous pustulosis (AGEP). Recent evidence demonstrated that the human 
      leukocyte antigen (HLA) polymorphisms play important roles in the development of 
      drug-related SCARs. This study aimed to extensively characterize the associations 
      between HLA genetic polymorphisms and several phenotypes of SCARs related to 
      beta-lactam antibiotics. Methods: Thirty-one Thai patients with beta-lactam 
      antibiotics-related SCARs were enrolled in the study. A total of 183 unrelated 
      native Thai subjects without any evidence of drug allergy were recruited as the 
      control group. Genotyping of HLA class I and class II alleles was performed. 
      Results: Six HLA alleles including HLA-A*01:01, HLA-B*50:01, HLA-C*06:02, 
      HLA-DRB1*15:01, HLA-DQA1*03:01, and HLA-DQB1*03:02, were significantly associated 
      with beta-lactam antibiotics-related SCARs. The highest risk of SCARs was 
      observed in patients with the HLA-B*50:01 allele (OR = 12.6, 95% CI = 1.1-142.9, 
      p = 0.042), followed by the HLA-DQB1*03:02 allele (OR = 5.8, 95% CI = 1.5-22.0, p 
      = 0.012) and the HLA-C*06:02 allele (OR = 5.7, 95% CI = 1.6-19.9, p = 0.011). 
      According to the phenotypes of SCARs related to beta-lactam antibiotics, the 
      higher risk of SJS/TEN was observed in patients with HLA-A*03:02, HLA-B*46:02 (OR 
      = 17.5, 95% CI = 1.5-201.6, p = 0.033), HLA-A*02:06, HLA-B*57:01 (OR = 9.5, 95% 
      CI = 1.3-71.5, p = 0.028), HLA-DQB1*03:02 (OR = 7.5, 95% CI = 1.8-30.9, p = 
      0.008), or HLA-C*06:02 (OR = 4.9, 95% CI = 1.1-21.4, p = 0.008). While eight HLA 
      alleles including HLA-A*02:05, HLA-A*02:11, HLA-B*37:01, HLA-B*38:01, 
      HLA-B*50:01, HLA-C*06:02, HLA-C*03:09, and HLA-DRB1*15:01 were associated with 
      AGEP, the highest risk of AGEP was observed in patients with the HLA-B*50:01 
      allele (OR = 60.7, 95% CI = 4.8-765.00, p = 0.005). Among the four HLA alleles 
      associated with DRESS including HLA-C*04:06, HLA-DRB1*04:05, HLA-DRB1*11:01, and 
      HLA-DQB1*04:01, the HLA-C*04:06 allele had the highest risk of beta-lactam 
      antibiotics-related DRESS (OR = 60.0, 95% CI = 3.0-1202.1, p = 0.043). However, 
      these associations did not achieve statistical significance after Bonferroni's 
      correction. Apart from the HLA risk alleles, the HLA-A*02:07 allele appeared to 
      be a protective factor against beta-lactam antibiotic-related SCARs (OR = 0.1, 
      95% CI = 0.0-0.5, p = 3.7 x 10(-4), Pc = 0.012). Conclusion: This study 
      demonstrated the candidate HLA alleles that are significantly associated with 
      several phenotypes of beta-lactam antibiotics-related SCARs. However, whether the 
      HLA alleles observed in this study can be used as valid genetic markers for SCARs 
      related to beta-lactam antibiotics needs to be further explored in other 
      ethnicities and larger cohort studies.
CI  - Copyright (c) 2023 Wattanachai, Amornpinyo, Konyoung, Purimart, Khunarkornsiri, 
      Pattanacheewapull, Tassaneeyakul and Nakkam.
FAU - Wattanachai, Pansakon
AU  - Wattanachai P
AD  - Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 
      Thailand.
FAU - Amornpinyo, Warayuwadee
AU  - Amornpinyo W
AD  - Division of Dermatology, Department of Internal Medicine, Khon Kaen Hospital, 
      Khon Kaen, Thailand.
FAU - Konyoung, Parinya
AU  - Konyoung P
AD  - Pharmacy Unit, Udon Thani Hospital, Udon Thani, Thailand.
FAU - Purimart, Danklai
AU  - Purimart D
AD  - Pharmacy Unit, Udon Thani Hospital, Udon Thani, Thailand.
FAU - Khunarkornsiri, Usanee
AU  - Khunarkornsiri U
AD  - Pharmacy Unit, Udon Thani Hospital, Udon Thani, Thailand.
FAU - Pattanacheewapull, Oranuch
AU  - Pattanacheewapull O
AD  - Pharmacy Department, Khon Kaen Hospital, Khon Kaen, Thailand.
FAU - Tassaneeyakul, Wichittra
AU  - Tassaneeyakul W
AD  - Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 
      Thailand.
FAU - Nakkam, Nontaya
AU  - Nakkam N
AD  - Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 
      Thailand.
LA  - eng
PT  - Journal Article
DEP - 20230919
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10546186
OTO - NOTNLM
OT  - Human Leukocyte Antigen
OT  - Stevens-Johnson syndrome/toxic epidermal necrolysis
OT  - acute generalized exanthematous pustulosis
OT  - beta-lactam antibiotics
OT  - drug reactions with eosinophilia and systemic symptoms
OT  - severe cutaneous adverse reactions
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/05 06:44
MHDA- 2023/10/05 06:45
PMCR- 2023/09/19
CRDT- 2023/10/05 04:02
PHST- 2023/06/27 00:00 [received]
PHST- 2023/08/31 00:00 [accepted]
PHST- 2023/10/05 06:45 [medline]
PHST- 2023/10/05 06:44 [pubmed]
PHST- 2023/10/05 04:02 [entrez]
PHST- 2023/09/19 00:00 [pmc-release]
AID - 1248386 [pii]
AID - 10.3389/fphar.2023.1248386 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Sep 19;14:1248386. doi: 10.3389/fphar.2023.1248386. 
      eCollection 2023.