# Rheumatoid Arthritis-Related Autoantibodies, Articular Inflammation, and RA-Associated Interstitial Lung Disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $814,364

## Abstract

PROJECT SUMMARY
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting nearly 1% of adults causing a painful,
destructive inflammatory arthritis with serious long-term consequences including chronic pain, disability,
accumulation of morbidities, and excess mortality. Patients with RA are susceptible to developing interstitial
lung disease (ILD), a devastating complication with high morbidity and mortality. Rheumatoid factor (RF) and
anti-cyclic citrullinated peptide (ant-CCP) autoantibodies are elevated in the serum of two-thirds of patients with
RA. Seropositive RA patients are more likely to develop RA-ILD. Previous studies suggest that mucosal
surfaces of the lung may be an initiating site for RA, after smoking or exposure to other inhalants, where RF,
anti-CCP, and other autoantibodies may be formed years before joint symptoms develop. Aberrant post-
translational modifications (PTM) to proteins may serve as neoantigens forming local inflammation in the lungs
and production of autoantibodies related to PTM. This site of lung injury may later manifest clinically as RA-ILD
and articular inflammation may impact risk for subclinical RA-ILD through systemic inflammation. Therefore,
RA-related autoantibodies, articular inflammation, and RA-ILD may be linked throughout the disease course of
RA.
These investigations will study whether RA-related autoantibodies and articular inflammation predict subclinical
and clinically-apparent RA-ILD. In the first aim, we will perform a nested case-control study using a derivation
dataset in the Brigham RA Sequential Study (BRASS) and a replication dataset in the Partners Biobank.
BRASS and the Partners Biobank are patient registries for research. We have identified RA-ILD cases as well
as controls with RA but no ILD in these research registries and propose to measure clinical and PTM RA-
related autoantibodies. In the second aim, we will perform a multi-site prospective observational study of
patients with new-onset RA who will undergo serial measures of articular inflammation and chest high-
resolution computed tomography imaging to evaluate whether the burden of articular inflammation in early RA
reflects risk for subclinical RA-ILD. In the third aim, we will analyze whether smokers in COPDGene with
elevation of RA-related autoantibodies without articular RA are more likely to have subclinical ILD. COPDGene
is a large US nationwide observational study that has already been phenotyped for presence or absence of ILA
on chest computed tomography imaging.
Dr. Jeffrey Sparks (the PI) is an Assistant Professor of Medicine at Brigham and Women’s Hospital and
Harvard Medical School. He is an early-stage investigator previously funded by NIAMS through K23 and R03
awards to investigate the role of the lung in RA etiology and outcomes. These proposed studies will interrogate
the overarching hypothesis that RA autoimmunity, articular inflammation, and ILD are intrinsically linked across
the disease course of ...

## Key facts

- **NIH application ID:** 10207955
- **Project number:** 1R01AR077607-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jeffrey Andrew Sparks
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $814,364
- **Award type:** 1
- **Project period:** 2021-09-27 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207955

## Citation

> US National Institutes of Health, RePORTER application 10207955, Rheumatoid Arthritis-Related Autoantibodies, Articular Inflammation, and RA-Associated Interstitial Lung Disease (1R01AR077607-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10207955. Licensed CC0.

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