Identifying Genetic Variants in Patients With Cefaclor-Induced Anaphylaxis Using Human Leukocyte Antigen Typing and...

Area of Science:

• Pharmacogenomics
• Immunogenetics
• Drug Hypersensitivity

Background:

• Cefaclor, a common beta-lactam antibiotic, is a significant cause of immediate drug hypersensitivity in Korea.
• Genetic factors influencing cefaclor-induced anaphylaxis are not well understood.
• Identifying these genetic factors is crucial for understanding and managing severe allergic reactions.

Purpose of the Study:

• To identify genetic variants associated with cefaclor-induced anaphylaxis.
• To evaluate the clinical implications of these genetic variants.
• To explore potential genetic risk factors for beta-lactam allergy.

Main Methods:

• Whole-exome sequencing and HLA genotyping were performed on patients with cefaclor-induced anaphylaxis and drug-tolerant controls.
• Association analyses were conducted using logistic regression.
• Gene set enrichment analysis (GSEA) investigated relevant biological pathways.

Main Results:

• A rare missense variant (rs765144578) in TPSAB1 was strongly associated with anaphylaxis and reaction severity, particularly hypotension.
• A significant association was observed for rs192498095 in HLA-DRB5 in the discovery cohort.
• The co-occurrence of variants in TPSAB1 and HLA-DRB5 markedly increased anaphylaxis risk. GSEA highlighted the TNF-α signaling pathway.

Conclusions:

• Genetic variants in TPSAB1 and HLA-DRB5 may contribute to cefaclor-induced anaphylaxis risk.
• The TPSAB1 variant may also be linked to the severity of cefaclor-induced anaphylaxis.
• These discoveries could inform future screening strategies and personalized risk prediction for beta-lactam allergy.