Background/Purpose: Remission in Systemic Lupus Erythematosus (SLE) is described by the Definition of Remission in SLE (DORIS), but it is hardly achieved in clinical practice, while Lupus Low Disease Activity State (LLDAS) is easier achieved by a larger proportion of patients. Lupus flares negatively impact patient outcomes and survival. Only 24-hour urine protein (24hUP), anti-double-stranded DNA antibodies (anti-dsDNA) and serum complement components (C3) have been described as predictors of lupus flares [1]. Lately, the neutrophil-to-lymphocyte ratio (NLR) has emerged as potential biomarker of SLE activity and some studies have showed a correlation between NLR and lupus flares [2]. Since the lupus manifestations vary across different populations, can NLR be used as a biomarker to predict flares in the Mexican-Mestizo SLE patients under remission?To explore the usefulness of NLR as a biomarker to predict lupus flares in patients under remission.

Methods: A retrospective cohort study including patients over 18 years of age with a diagnosis of SLE according to the SLICC 2012 criteria, who achieved LLDAS and DORIS remission for more than two years. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was used to assess disease activity. NLR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), SLEDAI-2k, 24hUP, anti-dsDNA, and C3 were compared between patients with and without lupus flares. Correlations between NLR and previous variables were analyzed. Receiver operating characteristic (ROC) analysis was performed to determine the best NLR cutoff value for detecting lupus flares. Test characteristics, including sensitivity and specificity were calculated. A Cox proportional hazards model (CHM) was conducted to evaluate lupus flares risk with NLR as a predicting factor, reporting hazard ratio (HR) and 95% confidence intervals (95% CI).

Results: Of the 250 patients with SLE, 76 (30.4%) and 40 (16%) achieved LLDAS and DORIS remission, respectively. The most common lupus manifestation was articular (64.5%), followed by cutaneous (53.9%) and renal involvement (46.1%). A total of 13 (17.1%) patients experienced lupus flares, followed for a mean of 2.7 years (SD 0.35), across 912 visits. Of these, 46.2% had renal flares and 38.5% had articular flares. Patients with lupus flares more frequently had hypocomplementemia, and higher levels of anti-dsDNA, 24hUP, and CRP compared to patients without lupus flares (p=0.001). The median (IQR) NLR was higher in lupus flares patients than in those without flares [3.57 (2.74-4.36) vs 1.71 (1.40-2.34); p=< 0.001]. NLR had a moderate correlation with SLEDAI-2K (r=0.411; p=< 0.001). The NLR cut-off value was 2.59, and the area under the curve was 0.928, with 84.6% of sensitivity and 85.7% of specificity (Figure 1). In CHM, NLR > 2.59 (HR 6.45; 95% CI, 1.10-37.1; p= 0.039) was an independent factor associated with lupus flares during the follow-up (Figure 2).

Conclusion: This study suggests that NLR can be a useful and low-cost biomarker to predict lupus flares in patients under remission. However, these observations must be confirmed in larger and prospective studies.Fatemi A et al. BMC Rheumatol 2023;7(1):10.Predescu OR et al. Curr Health Sci J 2024;50(3):347.

Figure 1. Receiver operating characteristic (ROC) curve analysis of neutrophil-to-lymphocyte ratio (NLR) to predict lupus flares in patients under remission. For NLR, the cut-off value was 2.59, and the area under the curve was 0.928 (95% confidence intervals: 0.856-0.997; p= < 0.001), with sensitivity, specificity, and diagnostic accuracy of 84.6%, 85.7%, and 85.5% respectively.

Figure 2. Multivariate Cox regression analysis using the Cox proportional hazards model was conducted to evaluate the risk of lupus flares, establishing NLR as predictive factor.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-usefulness-of-neutrophil-to-lymphocyte-ratio-as-a-biomarker-to-predict-lupus-flares-in-patients-under-remission/