Background/Purpose: Neutrophils play a crucial role in pathogenesis of systemic lupus erythematosus (SLE). Recently, neutrophil to lymphocyte ratio (NLR) has been studied as a biomarker for various rheumatic diseases including in SLE. The aim of the current study was to evaluate if NLR reflects underlying pathogenetic mechanisms including reactions driven by immune complex (IC) in SLE.

Methods: Clinical information including peripheral blood cell counts, SLE disease activity index (SLEDAI), autoantibody (autoAb) profiles, complement levels, and treatment were collected for 104 SLE patients through the University of Washington (UW) Lupus Repository. Univariate and multivariate linear regression analyses were performed to determine associations between NLR and these variables, including clinical SLEDAI (calculated by subtracting any score for anti-dsDNA and complement from total SLEDAI). A second SLE cohort (n=143), recruited from Lund University (LU), Sweden, was included to investigate associations between NLR and immunological and inflammatory markers, serum type I interferon (IFN) activity as measured by a reporter cell system, and neutrophil subpopulations. For theses analyses, high NLR was defined as above 90th percentile of healthy individuals, and Mann-Whitney U test and logistic regression analyses were performed. 

Results: In the first cohort from UW, log-transformed NLR levels were significantly associated with clinical SLEDAI, anti-dsDNA, number of autoAbs, C3, C4, and prednisone dose in univariate analyses. In multivariate analyses, anti-dsDNA remained significantly associated with NLR (β= 0.3, p = 0.003) after controlling for age, gender, clinical SLEDAI, and prednisone dose. Among anti-DNA positive patients, NLR was independently associated with low C3 (β= 0.3, p = 0.02). In the second cohort from LU, high NLR correlated with increased circulating immune complexes (p=0.02) and downstream type I IFN activity (OR=2.3, p=0.04). Lastly, we observed a strong association between high NLR and elevated levels of the serum neutrophil activation marker, S100A8/A9 (p=0.001), and enrichment for low-density granulocytes (LDGs, p=0.001), a neutrophil subset known to be pathogenic in SLE patients.

Conclusion: Our findings support an association in SLE patients between NLR and markers of IC-driven inflammation, including anti-dsDNA, low C3, and type I IFN activity. Additionally, high NLR may reflect abnormal production of immature LDGs, known to promote inflammation and organ damage. Further studies are needed to determine the significance and underlying mechanisms of elevated NLR in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neutrophil-lymphocyte-ratio-as-a-marker-for-immune-complex-driven-inflammation-in-patients-with-systemic-lupus-erythematosus/