A recent study published in the journal PNAS suggests a potential new biomarker for the identification of rheumatoid arthritis (RA) patients who are unlikely to respond to methotrexate therapy. The study is entitled “Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis.”
Although it is not entirely clear how it works, methotrexate (MTX) is considered one of the first-line therapies for RA as it reduces inflammation and slows disease progression. However, around 40% of RA patients develop resistance to MTX, and this resistance is only detected after prolonged treatment (more than 3 months), which could mean that during this time, the health condition of MTX-resistant patients may have worsened. It is therefore important to find a viable biomarker for the identification of MTX-resistant patients so that they can be switched to an alternative therapy sooner rather than later.
Regulatory T cells have been suggested to be involved in attenuation of RA. In order to determine whether there is a link between the two, the researchers recruited 122 RA patients who were on MTX therapy (14 to 20 mg per week) for a period of at least four weeks. Healthy individuals were also recruited as controls. Of the 122 patients, 69 were non-responsive to MTX treatment. Three months after the treatment, these patients exhibited higher levels of inflammatory cytokines in comparison with patients responsive to MTX or healthy controls. In addition, researchers found that patients responsive to MTX showed higher frequencies of peripheral blood regulatory T cells, namely CD39+ T cells, indicating the possibility that the therapeutic effect of MTX is linked to an increase in circulating regulatory T cells. Indeed, non-responsive patients were found to express lower levels of CD39+ T cells. Interestingly, in an RA mouse model, the blockage of CD39+ T cells aborted the anti-arthritic effect of MTX treatment.
The team concluded that a low expression of CD39 in regulatory T cells in RA patients is responsible for their non-responsiveness to MTX therapy, and suggests that this low density of CD39+ T cells could be used as a potential, noninvasive, reliable biomarker for the identification of MTX-resistance in RA patients.
RA is an autoimmune disease that leads to chronic inflammation of the joints and other parts of the body. In the United States, it is estimated that about 1.5 million people suffer from this disease, with women having a significantly higher susceptibility.