# Project 2: Assessing Brain Dysfunction in Clinically Quiescent SLE

> **NIH NIH P01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $1,003,698

## Abstract

Abstract – Project 2
The overall goals of Project 2 are to localize and quantify patterns of central nervous system
(CNS) dysfunction in SLE patients in long-term clinical remission (SLE-R) and to identify a
relevant imaging marker. This has important potential treatment implications as our preliminary
data suggest that, despite clinical quiescence, some SLE-R have ongoing CNS dysfunction that
may promote progressive cognitive decline and contribute to relapse. Our Specific Aims are:
1. to investigate regional brain metabolism using FDG PET, blood brain barrier permeability
(BBBP) using dynamic contrast enhanced MRI (DCE MRI), neuropsychological (NP)
performance and serum Quinolinic/Kynurenic acid ratio (Q/K; a marker of CNS
pathology) in SLE-R,
2. to investigate microglial (MG) activation in SLE-R using [11C]-PBR28 PET, and
3. to identify and validate a SLE-R functional brain network using resting state functional
MRI (rs-fMRI) and to evaluate associations between the SLE-R network and NP
performance, Q/K ratios and risk of relapse.
A subgroup of eligible subjects from Project 1, 60 SLE-R, 20 SLE with active disease (SLE-A)
and 31 healthy controls (HC), will all have imaging studies, NP testing and serum Q/K evaluated
at baseline. SLE-R subjects will have repeat evaluations after 18-24 months and/or at the time
of clinical relapse. CNS subjects will be recruited at all sites and will include White, Black, Asian
and Hispanic individuals. The planned analyses will allow us to develop neurophenotypes,
defined by imaging measures, Q/K ratio and NP performance, for SLE-R. We expect to identify
a range of neurophenotypes among SLE-R; some SLE-R will resemble HC, others will resemble
SLE-A and perhaps others will have a phenotype that correlates with relapse. In collaboration
with the Biostatistics and Data Integration Core we will further explore the heterogeneity among
SLE-R neurophenotypes and associations with the immune phenotypes identified in Project 1.

## Key facts

- **NIH application ID:** 10763691
- **Project number:** 1P01AI172523-01A1
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** MEGGAN MACKAY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,003,698
- **Award type:** 1
- **Project period:** 2024-05-09 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763691

## Citation

> US National Institutes of Health, RePORTER application 10763691, Project 2: Assessing Brain Dysfunction in Clinically Quiescent SLE (1P01AI172523-01A1). Retrieved via AI Analytics 2026-07-20 from https://api.ai-analytics.org/grant/nih/10763691. Licensed CC0.

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