Predicting RA’s Silent Companion: ILD

By Vandana Suresh | May 13, 2025

Living with rheumatoid arthritis (RA) often means frequent pain, unpredictable flares and — if not managed properly — joint damage. In addition to these and other symptoms, comorbidities are quite common in RA patients, with many experiencing cardiovascular, lung and kidney diseases that negatively impact their health outcomes. Despite these coexisting and potentially debilitating health conditions, the emphasis of research has often been placed on RA rather than its comorbidities.

To focus on RA comorbidities, the Arthritis Foundation has given a RA Research Program award to Jeffrey Sparks, MD, MMSc, associate professor of medicine at Brigham and Women’s Hospital. With this funding Dr. Sparks and his team will look for cellular biomarkers to better diagnose, monitor and predict interstitial lung disease (ILD), a comorbidity associated with RA. In the near future, this research could lead to the discovery of novel therapeutic targets to treat RA-ILD.

“There’s been incredible advances in RA treatments over the past few decades. However, even with these expanded options, ILD in RA patients has not seemed to improve,” says Dr. Sparks. “We really need to figure out who is getting ILD and who is getting progressively worse, and certainly treatments that are going to help people with lung disease and RA.”

ILD could arise from the same inflammatory processes that have gone awry in RA. The disease is marked by scarring and inflammation of the lung tissue and can cause shortness of breath, dry cough and fatigue. There are, however, some known risk factors for RA-ILD, such as high RA disease activity, smoking, age and sex — a man is more likely to get RA-ILD than a woman, despite RA being three times more common in women. However, the impact of ILD on a patient can vary.

“It is a spectrum; some people have mild severity whereas others have severe ILD,” says Dr. Sparks. “As an estimate, 8 to 12% of people with RA have clinically relevant ILD that is diagnosed.”

Some patients might even progress to the point that they need supplemental oxygen or a lung transplant. An even more sobering observation is that RA-ILD prevalence has increased two-fold and is one of the few RA outcomes that is not improving. 

“Many of these patients are on medications for RA, and so their joints are not getting worse, but their lungs are, and ILD continues to progress in some,” says Dr. Sparks. 

There is an immediate need to identify which patients will get ILD and how the disease progresses.

For their Foundation-funded research, Dr. Sparks and his team, along with co-principal investigators Edy Kim, MD, PhD, and Kevin Wei, MD, PhD, both assistant professors of medicine at Harvard Medical School, will avail themselves of the ongoing Study of Inflammatory Arthritis and ILD in Early RA, or SAIL-RA, in which the patients enrolled have early RA. Enrollees will get routine CT scans over two years, so that the investigators can look for abnormal lung features at the very beginning of the disease process. These screening strategies could facilitate finding anatomical biomarkers that are early in the disease and halt ILD early in its tracks. Combined with the CT scan analysis, researchers will look for cellular biomarkers using RNA sequencing of different types of cells circulating in the blood that would be telltale signs of ILD presence and progression. 

“We are so excited about the Arthritis Foundation grant,” says Dr. Sparks. “This has been a cross-disciplinary collaboration that includes several sites and investigators, and the grant has played an important role in bringing the project together.”