Associations between neutrophil-to-lymphocyte ratio and autoimmune diseases: evidence from a large prospective cohort study

Authors

• D Yoon
• MA Beydoun
• LJ Launer
• M Song

Abstract

OBJECTIVES: Neutrophils and lymphocytes play crucial roles in immune system regulation and may be associated with the development and progression of autoimmune diseases. While the neutrophil-to-lymphocyte ratio (NLR) is an important emerging indicator of inflammation, evidence is limited by cross-sectional associations and sample sizes.
METHODS: We conducted a prospective cohort study among participants who completed blood count measures within the UK Biobank. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for per quartile increase of NLR, quantifying their associations with overall and 41 specific autoimmune diseases using Cox regression models. We adopted a 2-year lag-time to minimize reverse causality with Benjamini-Hochberg adjustments for multiple comparisons. Subgroup analyses were conducted to identify heterogeneity by sex.
RESULTS: Among 446,224 participants (mean age: 56.4, female: 54.1%, median time-to-diagnosis: 8.1 years), higher NLR was significantly associated with overall autoimmune diseases (33,224 events, HR: 1.11, 95% CI: 1.10-1.12). Of 41 specific autoimmune diseases, 27 positive associations and two inverse associations were observed. The strongest associations per quartile NLR increase were for sarcoidosis (1.52, 1.41-1.64), scleroderma (1.45, 1.10-1.92), and antiphospholipid syndrome (1.43, 1.24-1.65); Primary biliary cholangitis (0.87, 0.76-0.98) and pure red cell aplasia (0.41, 0.21-0.83) presented inverse associations. In subgroup analysis, ankylosing spondylitis (male: 1.29, 1.16-1.43 vs. female:1.09, 0.97-1.23; p-for-heterogeneity<0.05) and Crohn’s disease (1.33, 1.22-1.46 vs. 1.14, 1.06-1.23; p-for-heterogeneity<0.05) showed significant sex differences.
CONCLUSIONS: We report prospective associations between NLR and various autoimmune diseases, indicating its potential as a pre-clinical marker of inflammation and aiding in early diagnosis and risk assessment for these conditions.

Scientific Focus Area: Epidemiology

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