OBJECTIVES: Autoimmune diseases are characterized by inflammation and immune dysregulation. The neutrophil-to-lymphocyte ratio (NLR) is proposed as an indicator of balancing between innate and adaptive immunity, suggesting its relevance to autoimmune diseases. While some studies have highlighted the potential utility of NLR in specific autoimmune diseases, its role across a broader range of these conditions has not been fully elucidated.

METHODS: Using the UK Biobank database, we conducted a prospective cohort study among participants recruited between 2006 and 2010 who completed white blood cell count measurements. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for per quartile increase in NLR levels, quantifying their associations with overall and 41 types of specific autoimmune diseases using Cox regression models. We adopted a 2-year lag period to minimize reverse causality with Benjamini-Hochberg method adjusting for multiple comparisons of autoimmune diseases. Subgroup analysis was conducted to identify sex differences across specific autoimmune diseases.

RESULTS: Among 446,224 participants (mean age: 56.4, female: 54.1%, median time-to-diagnosis: 6.1 years), we found that higher NLR was significantly associated with overall autoimmune diseases (33,224 events, HR 1.11, 95% CI 1.10-1.12). Strongest associations were observed with 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, erythema nodosum (1.40, 1.03-1.89) and systemic lupus erythematosus (1.31, 1.18-1.46), revealed significant association only in females, whereas 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 significantly higher association in males.

CONCLUSIONS: To our knowledge, this is the first study with a comprehensive assessment of associations between NLR and multiple autoimmune diseases, indicating its potential as a pre-clinical indicator of inflammation and aiding in early diagnosis and risk assessment for these conditions.