# Defining how microbes drive abnormal T Cell responses in rheumatoid arthritis

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2024 · —

## Abstract

Rheumatoid arthritis (RA) is a debilitating disease that causes inflammation and deforming joint destruction.
RA afflicts 1.5 million people in the United States and is becoming increasingly more prevalent in the veteran
community as this population ages. It is also one of the most expensive illnesses to treat, resulting in hundreds
of millions of dollars in increased health care spending by the Veteran Administration (VA). The underlying
cause of RA remains unclear. Infections driving a misdirected response to self-proteins has been hypothesized
to underlie RA and other autoimmune diseases, but why some people remain healthy whereas others develop
autoimmunity remain poorly understood. Using SARS-CoV-2 infection as a model, we will investigate RA-
related differences in immune composition before exposure and determine how it responds to infection. The
proposed study will test the overarching hypothesis that disrupted interaction with the microbiome in RA
patients amplifies cross-reactive SARS-CoV-2-specific T cells at baseline, which contributes to
broadening of T cell and antibody responses after SARS-CoV-2 infection. In Aim 1, we will determine how
pre-existing cross-reactive responses change in patients with RA. We have recently demonstrated that CD4+ T
cells from healthy adults are capable of recognizing SARS-CoV-2 prior to exposure. Further, a subset of
SARS-CoV-2 specific precursors respond to commensal bacteria. Building on this, we will determine if the
basal level of T cell cross-reactivity becomes amplified in an autoimmune setting. In Aim 2, we will determine
how COVID-19 impacts cross-reactive responses. We will test if infection drives further expansion of cross-
reactive T cells in RA patients and define the relationship between the breadth of CD4+ T cells and antibody
responses. Data generated from these experiments will provide vital knowledge on SARS-CoV-2 specific T
cells and address fundamental questions on cross-reactive responses in humans. These findings will likely be
relevant beyond SARS-CoV-2 to inform cross-reactive responses to other pathogens.

## Key facts

- **NIH application ID:** 10696315
- **Project number:** 2I01CX001460-07
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Laura Su
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2016-07-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696315

## Citation

> US National Institutes of Health, RePORTER application 10696315, Defining how microbes drive abnormal T Cell responses in rheumatoid arthritis (2I01CX001460-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10696315. Licensed CC0.

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