# Molecular Imaging to Identify Neutrophil Activation in ANCA Vasculitis

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $253,845

## Abstract

Project Summary/Abstract
Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) is a systemic autoimmune disease caused by
pathogenic autoantibodies. The disease causes inflammation of small blood vessels in the kidneys, respiratory
tract, and other organs leading to irreversible organ damage. Current immunosuppressive treatment strategies
are often complicated by infections, adverse metabolic effects, infertility, and the development of
malignancies. AAV is marked by a relapsing course in many patients. Unfortunately, there are currently no
tools available to reliably predict the risk of disease relapse or response to treatment in individual patients.
This leads to large numbers of patients at low risk for disease relapse who are unnecessarily subjected to
prolonged courses of toxic treatment regimens.
Leukotrienes (LTs) are fatty acid mediators generated from arachidonic acid (AA) metabolism. The intracellular
assembly of 5-lipoxygenase (5-LO) and 5-lipoxygenase activating protein (FLAP) into the LT biosynthetic
complex on the nuclear envelope, and their subsequent generation of LTB4, has been observed in activated
neutrophils. Using fluorescence lifetime imaging microscopy (FLIM), we have generated preliminary data
demonstrating an increase in 5-LO/FLAP interactions in the setting of active AAV. We now seek to extend
these findings by determining if 5-LO/FLAP interactions can predict disease activity in a large cohort of patients
with AAV. In Aim 1, we investigate whether an increase in 5-LO/FLAP interactions precedes, and can
therefore predict, clinical disease flare. In Aim 2, we investigate whether treatment with
immunosuppression in patients with active AAV leads to an attenuation in 5-LO/FLAP interactions. The
knowledge gained may ultimately allow for tailoring of treatment regimens to disease activity on an individual
basis.

## Key facts

- **NIH application ID:** 9878745
- **Project number:** 5R21AI143612-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Angela Bair Schmider
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $253,845
- **Award type:** 5
- **Project period:** 2019-02-22 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878745

## Citation

> US National Institutes of Health, RePORTER application 9878745, Molecular Imaging to Identify Neutrophil Activation in ANCA Vasculitis (5R21AI143612-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878745. Licensed CC0.

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