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  • Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus

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Immunology and inflammation
Original research
Neutrophil and lymphocyte counts are associated with different immunopathological mechanisms in systemic lupus erythematosus
  1. Bobby Kwanghoon Han1,
  2. Katherine D Wysham2,
  3. Kevin C Cain3,
  4. Helena Tyden4,
  5. Anders A Bengtsson4 and
  6. Christian Lood1
  1. 1Department of Medicine, Division of Rheumatology, University of Washington, Seattle, Washington, USA
  2. 2Rheumatology Section, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
  3. 3Department of Biostatistics and Office for Nursing Research, University of Washington, Seattle, Washington, USA
  4. 4Department of Rheumatology, Lund University, Lund, Sweden
  1. Correspondence to Dr Christian Lood; loodc{at}uw.edu

Abstract

Objective Neutrophils contribute to the SLE pathogenesis. Neutrophil to lymphocyte ratio (NLR) is reported to correlate with disease activity in SLE. The aim of the study was to evaluate whether NLR reflects underlying immunopathogenic activity in SLE, as well as to determine the contribution of each component of NLR, neutrophil and lymphocyte count.

Methods Data were obtained from a cohort of patients with SLE (n=141) recruited at Lund University, Sweden. NLR levels were compared between patients with SLE and healthy controls (n=79). The relationship between NLR and clinical and immunological markers was examined using Mann-Whitney U test and logistic regression analysis. High NLR was defined as above the 90th percentile of healthy individuals.

Results Patients with SLE had elevated neutrophil count (p=0.04) and reduced lymphocyte count (p<0.0001), resulting in elevated NLR as compared with healthy controls (p<0.0001). Patients with high NLR had more active disease, and were more frequently on prednisone use and immunosuppressive medicines. High NLR was associated with immune complex (IC)-driven disease with presence of antidouble-stranded DNA antibodies (p=0.006), circulating ICs (p=0.02) and type I interferon (IFN) activity (p=0.009). Further, high NLR was associated with neutrophil abnormalities, including enrichment for low-density granulocytes (LDGs) (p=0.001), and increased levels of the serum neutrophil activation marker, calprotectin (p=0.02). Assessing the individual components within NLR, that is, neutrophil and lymphocyte count, high neutrophil count was associated with neutrophil activation markers (p<0.0001), whereas low lymphocyte count was associated with type I IFN activity and elevated numbers of LDGs (p=0.006 and p=0.001, respectively).

Conclusions NLR is elevated in patients with SLE as compared with healthy individuals, and is associated with key immunopathological events, including type I IFN activity and neutrophil activation. Neutrophil and lymphocyte count reflected different aspects of the pathogenesis of SLE. Further studies are needed to determine the causality of the associations.

  • systemic lupus erythematosus
  • interferon
  • autoimmune diseases
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/lupus-2020-000382

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    Footnotes

    • Contributors BKH, KDW and CL designed the study. BKH, AAB, HT and CL contributed with patients and data. KCC advised on the statistical analyses and interpretations. CL and BKH drafted the manuscript. KDW critically revised the manuscript. All authors read and approved the final version of the manuscript.

    • Funding The study was supported by the Lupus Research Alliance (#519414, CL).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study was approved by the Institutional Review Board at the Lund University (LU0601450), and informed consent was obtained from all participants.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.