Predicting Rheumatoid Arthritis Before Symptoms Begin   

Vandana Suresh | June 4, 2026   

Patients at risk for rheumatoid arthritis (RA) often find themselves in a grey zone, where their bloodwork indicates that they are at risk for RA, but cannot predict for certain whether they will get a clinical diagnosis. The presence of certain antibodies puts these patients at a 20% to 70% chance of developing clinical RA within two to five years, which is far from a definitive prognosis. 

Recognizing this gap, the Arthritis Foundation has awarded a 2025 RA Research Program grant to Marla Glass, PhD, a scientist at The Allen Institute in Seattle. With this grant, she will investigate how a type of immune cell, called a B cell, that makes antibodies evolves to become pathogenic, so some patients transition from preclinical (at-risk) RA to clinical RA. 

Understanding Preclinical RA 

“When it comes to individuals who are at risk, there have not been very many longitudinal studies performed where we have tracked features of their immune system over time. And, particularly amongst those individuals that convert to clinical RA, we have very limited information,” says Glass. “A major goal I have for my research is to essentially help us better understand a person’s risk for developing clinical RA and how we could think about therapeutic intervention for prevention of disease before it starts.” 

Before people start showing symptoms of RA, the immune system begins to display signs of dysfunction by producing autoantibodies, particularly those for cyclic citrullinated peptides (ACPA) and rheumatoid factors (RF). Antibody-producing B cells, part of the adaptive immune system, can undergo genetic changes to create highly specific receptors that can adapt to encounter new, unknown pathogens. At times, this adaptation can lead to either greater binding of B-cell receptors to proteins or increased inflammation. One or both of these mutations may be why some people develop RA.  

The Role of B Cells in RA Development 

Further, different types of B cells may contribute to the conversion from at-risk to clinical RA. Before the onset of clinical RA, memory B cells, or those that remember the characteristics of the protein that activated their parent B cell during initial infection, are present in large numbers. Therefore, these memory B cells are present in large numbers before (preclinical) and during (clinical) the onset of RA. At-risk individuals also have large populations of naive B cells that have not yet encountered their specific antigen. 

“That was a specific clue to us that something very important is likely happening with this cell type,” says Glass. “So generally, B cells have a lot of interactions that seem to be associated with the risk of conversion to clinical RA among those at-risk individuals. These observations motivated us to specifically focus on the evolution of pathogenic B cells as you progress to clinical RA.” 

In addition, B cells prime another very important cell type of the immune system, the T cells that are known to be the central drivers of inflammation and joint destruction in RA. In RA, it is possible that B and T cells can set up a feedback loop in which T cells encourage activation of B cells — and B cells, in turn, encourage activation of T cells. 

What This Research Could Mean for Patients 

For her Foundation-funded research, Glass will analyze blood samples from people at risk for RA, called single-cell multiomic profiling, some of whom eventually developed the disease. Using advanced molecular tools that can measure RNA and protein within individual cells, she will study how individual B cells behave and evolve over time in ACPA-positive individuals. In the future, she says, this work may improve risk assessment, identify new therapeutic targets and inform strategies to prevent disease before joint damage occurs. 

“I’m very thrilled to have gotten support for my research study from the Arthritis Foundation,” says Glass. “I think it’s going to enable us to kind of take our research to the next level and really provide some very deep insight into the preclinical phase of RA. I’m just very appreciative of the funding and to also be a part of this Arthritis Foundation network now.”