Growing evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) could complement traditional biomarkers in rheumatoid arthritis (RA) management by aiding early diagnosis, monitoring treatment response, and potentially predicting disease flares—particularly in resource-limited settings. Now, a recent study published in Medicine (Baltimore) further supports this potential, demonstrating that NLR is an independent predictor of RA diagnosis and disease activity, with notable utility in seronegative cases.
The retrospective single-center investigation analyzed 304 patients from the Department of Rheumatology and Immunology at a tertiary hospital between February 2021 and February 2024, comprising 201 RA patients and 103 non-RA controls. NLR levels were significantly higher in RA patients compared to non-RA controls (3.2 [2.1–4.8] vs 1.8 [1.2–2.3], P < .001). Multivariate regression analysis identified NLR as an independent predictor for RA diagnosis (odds ratio = 2.15, 95% CI: 1.62–2.85, P < .001), outperforming C-reactive protein and erythrocyte sedimentation rate. In seronegative RA, NLR retained significant diagnostic value (odds ratio = 2.01, 95% CI: 1.20–3.37, P = .008). NLR showed a positive correlation with disease activity and was notably higher in patients with moderate-to-high activity (4.2 [3.2–5.5], P < .001). Incremental analysis demonstrated that adding NLR to diagnostic models improved performance: in RA, the AUC increased from 0.89 to 0.94 (ΔAUC = 0.05, P < .001); in seronegative RA, the AUC rose from 0.72 to 0.82 (P = .002). For predicting disease activity, AUC improved from 0.85 to 0.91 (ΔAUC = 0.06, P = .004), with significant gains in net reclassification improvement and integrated discrimination improvement (0.18 and 0.07, respectively).
The NLR, calculated by dividing the absolute neutrophil count by the lymphocyte count from a routine complete blood count (CBC), has gained wide recognition as a valuable marker for assessing inflammatory activity in chronic inflammatory disorders such as ulcerative colitis and familial Mediterranean fever. A cross-sectional study by Chandrashekara et al. involving 489 rheumatoid arthritis patients found that the NLR correlated more closely with DAS28-CRP(3) than with CRP or ESR. Higher NLR was associated with worse pain, swollen joint counts, inflammatory parameters, and general health. An NLR cut-off of 1.4 identified deep remission with 90% specificity and 24% sensitivity. CRP predicted NLR, while interleukin-6 influenced CRP. NLR was concluded to be a cost-effective inflammation marker with efficacy comparable to CRP and less impact from cytokines affecting CRP and ESR.
The findings established NLR as a valuable inflammatory biomarker that enhanced diagnostic sensitivity and model discriminative ability across different RA phenotypes. The study concluded that NLR should be considered for promotion as a key diagnostic tool for early RA identification, particularly given its accessibility and cost-effectiveness compared to specialized autoantibody testing. The biomarker’s consistent performance across seropositive and seronegative RA cases positioned it as a potentially transformative addition to current diagnostic protocols in rheumatological practice.
References
- Yang X. The supplementary value of the neutrophil-to-lymphocyte ratio in the diagnosis of rheumatoid arthritis. Medicine (Baltimore). 2025 Jul 18;104(29):e43048.
- Mercan R, Bitik B, Tufan A, Bozbulut UB, Atas N, Ozturk MA, Haznedaroglu S, Goker B. The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis. J Clin Lab Anal. 2016 Sep;30(5):597-601.
- Chandrashekara S, Mukhtar Ahmad M, Renuka P, Anupama KR, Renuka K. Characterization of neutrophil-to-lymphocyte ratio as a measure of inflammation in rheumatoid arthritis. Int J Rheum Dis. 2017 Oct;20(10):1457-1467.