Mechanisms of Immediate Non-IgE-mediated Drug Hypersensitivity Reactions (MIND-HR)

Summary

This project aims to advance the understanding of non-IgE-mediated drug hypersensitivity reactions (HSRs), specifically those mediated by MRGPRX2, using vancomycin infusion reactions (VIR) as a model to develop diagnostic tools.

What they want

The project will conduct a multiphase study across three U.S. Allergy Centers. The UG3 Phase involves Aim 1 to validate a vancomycin skin test with an optimal concentration to discriminate VIR subjects (ROC ≥0.8) and Aim 2 to optimize and validate an immunofluorescence (IF)-based assay for quantifying MRGPRX2 in skin mast cells (reproducibility coefficient of variation <10%). Upon UG3 milestone accomplishment, the project will move to the UH3 Phase. Aim 3 will compare MRGPRX2 expression levels in sera and skin mast cells using the validated IF assay and correlate them with vancomycin skin test dose responses in VIR and vancomycin-tolerant subjects. Aim 4 will determine if VIR subjects exhibit skin hyperreactivity to other MRGPRX2 ligands.

Deliverables

Validated vancomycin skin test with ROC ≥0.8
Optimized and validated immunofluorescence (IF)-based assay for MRGPRX2 in skin mast cells (CV <10%)
Comparative data on MRGPRX2 expression levels in sera and skin mast cells between VIR and vancomycin-tolerant subjects
Correlation data between MRGPRX2 expression and vancomycin skin test dose responses
Determination of skin hyperreactivity to other MRGPRX2 ligands in VIR subjects
Advanced understanding of MRGPRX2-mediated drug HSR mechanisms
Comprehensive methodology for studying other non-IgE-mediated HSRs

Technical requirements

Vancomycin skin test validation with an ROC ≥0.8
Immunofluorescence (IF)-based assay for MRGPRX2 with a reproducibility coefficient of variation of <10%