Rheumatoid arthritis (RA) Trusted Source is an autoimmune condition that currently has no cure; however, researchers are trying to find ways to detect it early in hopes of preventing its progression. One area scientists have focused on is biomarkers in the blood.

Individuals with rheumatoid arthritis exhibit elevated levels of autoantibodies several years prior to the onset of the disease and its characteristic symptoms — such as pain and swelling in the joints. While these antibodies are useful in predicting whether a person will develop RA, a significant portion of individuals with these antibodies do not develop this condition.

A recent study published in the journal Science Translational Medicine characterized the changes in individuals’ immune systems as they progressed from being at risk of developing rheumatoid arthritis to actually showing clinical symptoms.

Characterizing this immune profile in at-risk individuals who progress to clinical rheumatoid arthritis could allow the early detection of this condition and the development of preemptive therapies for this at-risk population.

The study’s author, Gary Friestein, MD, senior associate vice chancellor for health sciences at the University of California, San Diego School of Medicine, said, “Most people who are at-risk for RA never develop the disease. That makes prevention studies difficult because some individuals who do not need therapy will be treated with medicines with potential side effects.”

“We hope that the findings from this study will directly support new ways to predict RA as well as potentially identify targets for prevention trials,” added the study’s co-author, Kevin Deane, MD, Professor of Medicine at the University of Colorado Anschutz.

The disease-modifying drugs used for the treatment of RA cannot reverse the damage, but can prevent the progression of the disease and help manage the condition. However, studies suggest that 5 to 27% of individuals with rheumatoid arthritis do not respond to these treatments, and relapse is also common after remission in individuals who respond to treatments.

Detecting rheumatoid arthritis early crucial

Individuals with rheumatoid arthritis exhibit elevated levels of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) 3-5 years prior to the onset of clinical symptoms. Approximately 30-60% of individuals with elevated ACPA and RF levels go on to develop rheumatoid arthritis. In other words, ACPA and RF levels are not accurate predictors of progression to RA.

Attempts are currently underway to develop preemptive treatments to prevent the development of rheumatoid arthritis in the at-risk population expressing ACPA and RF. For instance, studies have shown that the drug abatacept can reduce the risk of rheumatoid arthritis development in this at-risk population.

When cells become pro-inflammatory

The researchers were unable to detect any differences in gene or protein expression in immune cells between converters and non-converters at the start of the study.

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Immune profile of people who develop arthritis

The researchers then characterized changes within the group of converters from the time of their last visit without clinical symptoms to their next visit when they were first diagnosed with clinical RA. These changes in the immune profile of converters were compared with those in healthy controls over a similar time frame.

Autoimmune conditions are caused by the immune system’s failure to distinguish between the body’s own proteins and foreign proteins or antigens from germs. Autoimmune conditions are characterized by a dysfunction of T and B lymphocytes,Trusted Source which are crucial components of the immune system involved in producing a coordinated response in an antigen-specific manner.

In the present study, the researchers found changes in gene expression of B and T cells in converters, suggesting the activation or stimulation of these cells. Naive lymphocytes become activated upon their exposure to antigens, leading to their proliferation and differentiation into effector cells or memory cells. The short-lived effector cells are involved in the immediate immune response, whereas long-lived memory cells facilitate a faster response to future infections.

Naive or memory B cells are activated upon binding to an antigen, leading to their proliferation and differentiation into antibody-producing effector cells. In rheumatoid arthritis, subsets of B cells produce autoantibodies against the lining of joints.