Elevated neutrophil-to-lymphocyte ratio and the incidence of autoimmune diseases: evidence from a large prospective cohort study

TL;DR

High neutrophil-to-lymphocyte ratio is linked to increased risk of autoimmune diseases, suggesting it could help identify at-risk individuals early.

Contribution

This study provides large-scale evidence that elevated NLR is a pre-clinical indicator for multiple autoimmune diseases.

Findings

Elevated NLR was significantly associated with any autoimmune disease (HR per quartile increase: 1.09).

A non-linear association was observed, with risk increasing above an NLR threshold of 2.51.

14 out of 39 autoimmune diseases showed significant associations, including sarcoidosis and autoimmune hepatitis.

Abstract

We prospectively assessed the association between neutrophil-to-lymphocyte ratio (NLR) and incident autoimmune disease risk using data from 430,347 UK Biobank participants recruited between 2006 and 2010. The NLR was calculated by dividing neutrophil counts by lymphocyte counts and categorized into quartiles. Cox regression models estimated hazard ratios (HRs) for per quartile increase of (1) a composite of 39 types of autoimmune diseases, (2) each specific autoimmune diseases, applying a 2-year lag-period and Bonferroni adjustments. Natural cubic spline analysis was performed to assess the threshold of NLR associated with autoimmune diseases. Among 430,347 participants (mean age: 56.4 years, 53.9% female), elevated NLR was significantly associated with any autoimmune diseases (27,571 events, HR per quartile increase: 1.09, 95% CI: 1.08–1.10; P-trend < 0.01). A non-linear association was observed, with risk significantly increasing above an NLR threshold of 2.51. Participants in the highest quartile (Q4) had a higher risk compared to Q1 (HR 1.30, 95% CI 1.26–1.35). Of 39 autoimmune diseases, 14 showed significant associations, most notably sarcoidosis (HR 1.52, 95% CI 1.38–1.67), antiphospholipid syndrome (1.46, 1.26–1.69), and autoimmune hepatitis (1.37, 1.20–1.56). These findings suggest elevated NLR as a potential pre-clinical indicator for identifying individuals at increased risk of autoimmune diseases.

The online version contains supplementary material available at 10.1038/s41598-025-21188-y.

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