# IL-40 levels in treatment-naive and methotrexate-treated rheumatoid arthritis patients

## TL;DR

This study found that IL-40 levels are elevated in rheumatoid arthritis patients and remain high even after methotrexate treatment, suggesting a potential role in the disease's immune pathways.

## Contribution

The study identifies IL-40 as an independent predictor of rheumatoid arthritis, even in patients undergoing methotrexate therapy.

## Key findings

- IL-40 levels were significantly higher in both newly diagnosed and methotrexate-treated RA patients compared to healthy controls.
- IL-40 levels remained unchanged between newly diagnosed and methotrexate-treated RA patients, indicating resistance to treatment effects.
- TGF-β1 and TNF-α levels varied in seropositive and seronegative RA patients following methotrexate treatment.

## Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by persistent inflammation and progressive damage to the joints. In this study, it was aimed to explore the role of interleukin (IL)-40, a newly discovered cytokine, in the pathogenesis of RA. We also aimed to investigate the relationship between IL-40 and other cytokines such as IL-4, transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α.

This single-center, cross-sectional study included 87 participants divided into three groups: healthy controls (n = 29), newly diagnosed RA patients (n = 29), and RA patients with remission under methotrexate (MTX) monotherapy (n = 29). Serum samples were collected and analyzed for IL-40, IL-4, TGF-β1 and TNF-α levels using ELISA. Disease activity score, presence of autoantibodies and other relevant clinical data were obtained from hospital electronic records.

Elevated IL-40 levels were found in the newly diagnosed RA patients and in those treated with MTX compared to the control group (p < 0.001). Logistic regression analysis confirmed IL-40 as an independent predictor in the newly diagnosed (OR = 1.023, 95% CI: 1.010–1.035, p = 0.002) and RA MTX-treated patients (OR = 1.023, 95% CI: 1.011–1.036, p < 0.001). IL-40 levels remained unchanged in the newly diagnosed RA group compared to RA patients in the MTX-treated group. In the dual-seropositive patients, TGF-β1 was lower in the MTX-treated RA patients compared to the naive patients (p = 0.013) and in the dual-seronegative patients, TNF-α was decreased in the MTX-treated RA patients in comparison to naive patients (p = 0.043).

This study demonstrates that IL-40 levels are elevated in RA patients and highlights its potential role in RA. The fact that IL-40 levels did not change despite the antiinflammatory effects of MTX suggests that IL-40 is involved in immunological pathways that are less responsive to treatment.