Background Methotrexate and Etanercept are common treatment strategies for rheumatoid arthritis (RA) and are classified as conventional synthetic and biologic disease-modifying antirheumatic drugs respectively. Toll-like receptor-2 (TLR-2) is a transmembrane protein that plays a significant role in the innate immune and recognizes different patterns of molecules. This study aims to clarify the potential impact of these treatments on serum levels of soluble TLR-2 (sTLR-2) in RA patients, and explore the potential characteristics of sTLR‑2 as a candidate biomarker for monitoring therapeutic efficiency. Methodology Serum sTLR-2 levels were measured in 85 RA patients and 38 controls using an ELISA assay. Patients were categorized into three groups: 20 patients receiving methotrexate monotherapy, 40 receiving etanercept monotherapy, 25 receiving of combined therapy. Inflammatory tests: ACPA, ESR, CRP, and RF were measured. Demographic factors: age, BMI, DAS28-CRP, and disease duration were also evaluated. Results The mean of age and n (%) of sex for patients were matched to controls (P > 0.05). The mean ± SD of sTLR2 was elevated significantly in etanercept therapy group than the control (10.7 ± 4.9 vs7.8 ± 2.79, P = 0.03 respectively), and lowered in the methotrexate group (7.5 ± 2.89, P = 0.04) than etanercept group. Univariate logistic regression analysis showed that sTLR-2 had a significant predictive probability for RA disease development, (β: 0.119, OR: 1.126, P:0.045), significant predictive probability for potentially etanercept treatment response (β: 0.26, OR: 1.297, P: 0.004) and non-significant to methotrexate response (β: -0.035, OR: 0.965, P = 0.72). ROC analysis showed a fair accuracy for discrimination etanercept-treated RA patients from controls (AUC: 0.7, P: 0.0012, 95% sensitivity, 42.1% specificity at > 6.51 ng/ml cutoff value). Conclusions Circulating sTLR‑2 levels are differentially influenced by methotrexate and etanercept therapies in RA patients. Elevated sTLR‑2 in etanercept‑treated RA patients, together with its predictive probability and fair discriminatory accuracy, supports its potential as a biomarker for tracking the efficiency of etanercept monotherapy, but requires validation in larger longitudinal studies. In contrast, methotrexate showed no significant predictive association, underscoring sTLR‑2’s selective utility in biologic treatment evaluation.

Impact of methotrexate and etanercept drugs on serum levels of soluble toll-like receptor-2 in Iraqi patients with rheumatoid arthritis

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2026年4月21日

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Muna R. Hameed,
Faiq I. Gorial,
Fayhaa M. khaleel

摘要

Background

Methotrexate and Etanercept are common treatment strategies for rheumatoid arthritis (RA) and are classified as conventional synthetic and biologic disease-modifying antirheumatic drugs respectively. Toll-like receptor-2 (TLR-2) is a transmembrane protein that plays a significant role in the innate immune and recognizes different patterns of molecules. This study aims to clarify the potential impact of these treatments on serum levels of soluble TLR-2 (sTLR-2) in RA patients, and explore the potential characteristics of sTLR‑2 as a candidate biomarker for monitoring therapeutic efficiency.

Methodology

Serum sTLR-2 levels were measured in 85 RA patients and 38 controls using an ELISA assay. Patients were categorized into three groups: 20 patients receiving methotrexate monotherapy, 40 receiving etanercept monotherapy, 25 receiving of combined therapy. Inflammatory tests: ACPA, ESR, CRP, and RF were measured. Demographic factors: age, BMI, DAS28-CRP, and disease duration were also evaluated.

Results

The mean of age and n (%) of sex for patients were matched to controls (P > 0.05). The mean ± SD of sTLR2 was elevated significantly in etanercept therapy group than the control (10.7 ± 4.9 vs7.8 ± 2.79, P = 0.03 respectively), and lowered in the methotrexate group (7.5 ± 2.89, P = 0.04) than etanercept group. Univariate logistic regression analysis showed that sTLR-2 had a significant predictive probability for RA disease development, (β: 0.119, OR: 1.126, P:0.045), significant predictive probability for potentially etanercept treatment response (β: 0.26, OR: 1.297, P: 0.004) and non-significant to methotrexate response (β: -0.035, OR: 0.965, P = 0.72). ROC analysis showed a fair accuracy for discrimination etanercept-treated RA patients from controls (AUC: 0.7, P: 0.0012, 95% sensitivity, 42.1% specificity at > 6.51 ng/ml cutoff value).

Conclusions

Circulating sTLR‑2 levels are differentially influenced by methotrexate and etanercept therapies in RA patients. Elevated sTLR‑2 in etanercept‑treated RA patients, together with its predictive probability and fair discriminatory accuracy, supports its potential as a biomarker for tracking the efficiency of etanercept monotherapy, but requires validation in larger longitudinal studies. In contrast, methotrexate showed no significant predictive association, underscoring sTLR‑2’s selective utility in biologic treatment evaluation.