CIRCULATING INFLAMMATORY PROTEINS IN DRUG-INDUCED ANAPHYLACTIC SHOCK: EVIDENCE FROM MULTIVARIABLE MENDELIAN...

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Drug-induced anaphylactic shock (DIAS) is a significant clinical issue with increasing prevalence.
• The specific roles of circulating inflammatory proteins in DIAS pathogenesis are not well understood.

Purpose of the Study:

• To investigate the causal associations between circulating inflammatory proteins and the risk of DIAS.
• To identify potential biomarkers and therapeutic targets for DIAS.

Main Methods:

• Multivariable Mendelian randomization (MR) analysis was employed.
• Data from a European ancestry cohort (14,824 samples) for inflammatory proteins and the FinnGen consortium (20,806 cases, 411,845 controls) for DIAS were utilized.
• Complementary analyses included colocalization, enrichment studies, drug screening, and molecular docking.

Main Results:

• MR analysis revealed significant associations between specific inflammatory proteins and DIAS risk.
• CD40L demonstrated a protective effect (OR = 0.69).
• CXCL10 (OR = 1.51) and CCL3 (OR = 2.08) were significantly associated with increased DIAS risk.

Conclusions:

• Novel associations between inflammatory proteins and anaphylaxis risk were identified.
• These findings provide insights for developing targeted prediction and therapeutic strategies for DIAS.