Study Shows Rheumatoid Arthritis Begins Years Before Symptoms Appear
RA is a debilitating autoimmune disease that causes painful joint inflammation and damage.
The new research, published in the journal Science Translational Medicine, reveals that during the early phase of RA, the body fights an autoimmune battle invisibly.
This wasn't a localised joint inflammation, but rather a body-wide inflammatory state that resembles what's seen in people with active RA.
"Overall, we hope this study raises awareness that rheumatoid arthritis begins much earlier than previously thought and that it enables researchers to make data-driven decisions on strategies to disrupt disease development," said Mark Gillespie, assistant investigator at the Allen Institute, US.
During the seven-year study, researchers tracked several people carrying ACPA antibodies -- known biomarkers for individuals at risk for developing RA. They also identified previously unknown factors associated with disease development, including widespread inflammation, immune cell dysfunction, and cellular reprogramming.
The team found that among people at risk of RA, several types of immune cells had significant abnormalities. B cells, which normally produce protective antibodies, had shifted toward a pro-inflammatory state.
Further, T helper cells, particularly a subset resembling Tfh17 cells, were dramatically expanded beyond normal levels.
Perhaps most remarkably, the study found that even "naive" T cells -- immune cells that haven't encountered threats before -- showed epigenetic changes.
The researchers also identified monocytes (a type of white blood cell) in the bloodstream that were producing high levels of inflammatory molecules.
Significantly, these blood cells closely resembled the macrophages found in the inflamed joint tissue of RA patients, suggesting the disease process was already preparing to target joints.
The study reveals new early-warning signs (biomarkers and immune signatures) that could help doctors identify who among at-risk individuals is most likely to develop RA, enabling more targeted monitoring and earlier intervention.
If caught early, RA could be stopped before it starts -- saving patients years of pain and disability.

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