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Researchers identify potential biomarker for MTX non-responders in RA
Low expression of CD39 on regulatory T cells could be a biomarker for identifying patients with rheumatoid arthritis who will not respond well to treatment with methotrexate, according to study findings.
Researchers recruited 122 patients with rheumatoid arthritis (RA) who received therapy with methotrexate (MTX) at doses of 14 mg to 20 mg per week for at least 4 weeks. Thirty-three healthy controls were also recruited. Blood samples were collected after treatment — as well as prior to treatment in some patients — and disease activity was measured. No significant differences in demographic factors, time of disease onset, smoking habits or presence of rheumatoid factor or anti-citrullinated peptide antibodies were seen between groups.
After at least 3 months, 69 patients were identified as unresponsive to treatment (UR-MTX) and still presented with active disease.
Serum levels of inflammatory cytokines and frequencies of blood leukocyte subtypes were analyzed. UR-MTX patients showed significantly higher levels of serum tumor necrosis factor-alpha and interleukin-1 beta compared with MTX responders and healthy individuals, according to the researchers. MTX responders had higher frequency of IL-10-producing CD4+IL-17+, whereas UR-MTX patients had levels similar to healthy control participants.
The researchers also found UR-MTX patients had higher frequencies of regulatory T cells, suggesting that the therapeutic effect of MTX is associated with an increase in circulating regulatory T cells.
Upon further analysis, an association between low expression density of CD39 on regulatory T cells was observed in UR-MTX patients. In patients who responded to treatment, the frequency of CD39-expressing regulatory T cells was increased by treatment with MTX. In UR-MTX participants, lower density of CD39-expressing regulatory T cells were seen before treatment, suggesting the reduced levels may be a predictive biomarker for identifying patients who may not respond well to treatment with MTX, according to the researchers. – by Shirley Pulawski
Disclosures: The researchers report no relevant financial disclosures.