# Investigating a novel cell population in delayed-onset drug hypersensitivity reactions

> **NIH NIH DP5** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $412,750

## Abstract

Project Summary/Abstract
Delayed-onset drug hypersensitivity reactions (DHR) are a significantly under-recognized and under-
researched public health problem. Approximately 7% of the general population is affected by drug allergy. Skin
is the most commonly affected organ and severity ranges from a mild rash to severe blistering and sloughing
with internal organ involvement. The pathobiology of delayed-onset DHR is poorly understood due to a lack of
both usable clinical samples and mouse models that recapitulate human disease. This negatively impacts
patient care for 3 reasons. First, clinicians are ill-equipped to treat severe forms of disease. Second, there are
no effective assays to identify a culprit drug, which can result in administering a less effective, more
dangerous, and/or more-expensive drug in the future. Third, it can be difficult to discern drug allergy from other
diagnoses with negative bearing on patient prognosis and/or treatment. It is therefore of paramount
importance to elucidate the pathobiology of delayed-onset DHR to address these clinical needs. The
central hypothesis of this project is that a recently identified population of T cells, termed skin resident-memory
T cells (TRM), mediate delayed-onset DHR. The proposed project will directly test this hypothesis while
overcoming current limitations in the field. Aim 1 employs three novel technologies to study a large bank of
formalin-fixed paraffin embedded clinical specimens that until now were of little research utility. These
technologies are (i) PerkinElmer’s OpalTM multiplexed immunohistochemistry and MantraTM Quantitative
Pathology Workstation with inFORM® Image Analysis Software, (ii) NanoString technology for gene
expression profiling and (iii) ImmunoSEQ high-throughput TCR deep sequencing to assess TCR repertoire.
Aim 1 further includes laboratory investigation of prospectively collected clinical specimens, by taking
advantage of the patient volume of Harvard’s tertiary care hospitals. Aim 2 tests the role of skin TRM in delayed-
onset DHR ex vivo, and in-so-doing develops a much needed assay to diagnose drug allergy. Aim 3 leverages
progress in humanized mouse technology to study human skin TRM in an in vivo model of delayed-onset DHR,
thereby creating a mouse model of disease for future research. The data generated through this project will
advance both the fields of skin T cell biology and delayed-onset DHR.

## Key facts

- **NIH application ID:** 9993621
- **Project number:** 5DP5OD023091-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sherrie Jill Divito
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,750
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993621

## Citation

> US National Institutes of Health, RePORTER application 9993621, Investigating a novel cell population in delayed-onset drug hypersensitivity reactions (5DP5OD023091-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9993621. Licensed CC0.

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