# Supplement to Mechanisms of New-Onset Autoimmunity/Longitudinal Immune Systems Analysis (MONA-LISA)

> **NIH NIH U01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $216,290

## Abstract

PROJECT SUMMARY/ABSTRACT
The Mechanisms of New-Onset Autoimmunity-Longitudinal Immune Systems Analysis (MONA-LISA) will use
clinical data and biospecimens obtained during performance of the clinical trial, Study of Anti-Malarials in
Incomplete Lupus Erythematosus (SMILE, NCT03030118) to investigate immunological mechanisms that
propel individuals who have asymptomatic or minimally symptomatic autoimmunity towards a definite diagnosis
of systemic lupus erythematosus. These data and specimens are a unique resource, representing longitudinal
clinical assessments, patient-reported outcomes, DNA, RNA, serum, plasma, peripheral blood mononuclear
cells and urine obtained in a standardized manner before, during, and after the progression from Incomplete
Lupus Erythematosus to Systemic Lupus Erythematosus (SLE) – an observation that occurred in twenty
percent of the SMILE participants available for study. The overall objective of the study is to learn the
underlying immunological, genomic, and metabolic differences present in individuals who progress to SLE
compared to those that do not progress with goals to both develop better diagnostic and prognostic tools for
health care providers as well as describe novel therapeutic targets so that individuals with early features of
autoimmunity can be prevented from progressing to a state of organ damage and disability.
The Specific Aims of MONA-LISA include: 1) Obtain a comprehensive, multiplex analysis of the peripheral
blood immunophenotype of progressors and non-progressors in the SMILE cohort using a novel 137-plex
CITE-seq analysis, sn-ATAC-seq, sc-RNA-seq and T and B cell repertoire determination to create a robust,
quantitative atlas of cell-specific mRNA and epigenomic profiling in PBMC of these individuals. 2) Perform
targeted genomic sequencing to categorize regulatory and structural variants of SLE risk loci to tie together the
transcriptomic and epigenomic data and create novel risk assessments based on gene regulation. 3) Explore
plasma and serum metabolic and lipid components that can serve as novel features that classify the risk of
SMILE participants who progress towards classification with lupus. 4) Lastly, because SMILE enrolled fewer
Black individuals than are represented in the epidemiology of prevalent lupus patients, we will perform a
focused recruitment of non-European individuals with ILE and compare their multi-omic characterization of
immunophenotypes described in Aims 1-3. This will allow more complete and generalizable conclusions to be
drawn across ethnic groups and identify any ancestry-specific variations in the risk of autoimmunity
progression that can explain the observed differences in lupus epidemiology. When completed, MONA-LISA
will provide researchers and health care providers with better tools to predict who will develop lupus and create
more effective interventional trials for disease prevention.

## Key facts

- **NIH application ID:** 11099031
- **Project number:** 3U01AI176135-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Joel Marvin Guthridge
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,290
- **Award type:** 3
- **Project period:** 2023-03-22 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099031

## Citation

> US National Institutes of Health, RePORTER application 11099031, Supplement to Mechanisms of New-Onset Autoimmunity/Longitudinal Immune Systems Analysis (MONA-LISA) (3U01AI176135-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11099031. Licensed CC0.

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