Mechanisms of immediate non-IGE-mediated drug hypersensitivity reactions (mind-HR)
Active Cooperative Agreement Awarded Last action
- Award ID
- UG3AI190386
- Recipient
-
The University Of Texas Southwestern Medical Center UEI YZJ6DKPM4W63
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,315,675
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 68% complete
- Place of performance
- Dallas, TX 75390, USA
Award details come from USAspending.gov.
Description
- Abstract
- Although IGE-mediated hsrs are the most feared, most drug hsrs are non-IGE-mediated and often require only dosage and administration adjustments rather than complete drug avoidance. Clinical similarities between IGE- and non-IGE-mediated immediate hsrs lead to misclassification, unnecessary drug avoidance, less effective treatments, and increased costs. Recent research has emphasized the role of non-IGE receptors, such as MRGPRX2, in mast cell (MC) activation. MRGPRX2, expressed primarily on skin MCS, is a ligand for positively charged drugs like vancomycin, fluoroquinolones, and some neuromuscular blocking agents. MRGPRX2 activation requires sustained and high tissue drug concentrations, often surpassing therapeutic levels. This discrepancy may stem from differences in MRGPRX2 expression or functionality. IT is unknown if individuals with an MRGPRX2 ligand-mediated HSR exhibit elevated MRGPRX2 expression levels in sera and skin MCS or heightened sensitivity to other MRGPRX2 ligands, suggesting a definable hyperreactive phenotype. Using vancomycin infusion reactions (VIR) as a prototypical MRGPRX2 ligand-induced HSR, this proposal aims to compare MRGPRX2 expression levels in sera and skin MCS and skin test dose responses to other MRGPRX2 ligands in subjects with VIR compared to vancomycin-tolerant controls. The research rationale is based on preliminary data suggesting that VIR subjects have a significantly lower vancomycin skin test dose threshold for a positive response than vancomycin-tolerant subjects, raising the possibility that these individuals may also exhibit lower thresholds and increased sensitivity to other MRGPRX2 ligands. A multiphase study will be conducted by three U.S. Allergy centers. In the UG3 phase, aim 1 will validate a vancomycin skin test with an optimal vancomycin concentration to discriminate VIR subjects with an ROC ≥0.8. Aim 2 will optimize and validate an immunofluorescence (if)-based assay for quantifying MRGPRX2 in skin MCS with a reproducibility coefficient of variation of
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $101,217 | |
| Amendment | $394,205 | |
| Amendment | $394,205 | |
| Original award | $426,048 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Johns Hopkins University | $97,462 | |
| Vanderbilt University Medical Center | $110,462 |
Quick answers
Who received award UG3AI190386?
UG3AI190386 was awarded to The University Of Texas Southwestern Medical Center by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 23, 2025.
How much is award UG3AI190386 worth?
$1,315,675 has been obligated on UG3AI190386.
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