ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1596359
This article is part of the Research TopicNovel Biomarkers for Early Diagnosis, involved in Autoimmune and Autoinflammatory DiseasesView all 15 articles
Association between neutrophil percentage-to-albumin ratio and rheumatoid arthritis: a cross-sectional study from US population, 1999-2018
Provisionally accepted
- 1The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- 2Hunan University of Medicine, Huaihua, Hunan Province, China
- 3School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Background Rheumatoid arthritis (RA) is linked to systemic inflammation and immune dysregulation. The neutrophil-percentage-to-albumin ratio (NPAR), integrating neutrophil activity and nutritional status, may reflect inflammatory and immune responses. However, its association with RA remains unexplored. We aimed to investigate the relationship between the neutrophil-percentage-to-albumin ratio (NPAR) and rheumatoid arthritis (RA) using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.Methods This cross-sectional study utilized data from NHANES including 38,272 participants with RA. The NPAR was calculated based on the neutrophil percentage (in total WBC count) (%), and albumin value (g/dL). We employed weighted multivariable logistic regression analysis and subgroup analysis to examine the association between NPAR and RA, adjusting for sociodemographic, lifestyle, and clinical covariates.Restricted cubic splines were used to assess potential non-linear relationships.Additionally, receiver operating characteristic (ROC) was performed to determine the predictive accuracy of NPAR compared with other inflammatory markers.After adjusting for all covariates, multivariable logistic regression indicated that elevated levels of NPAR were significantly associated with an increased risk of RA (ORtertile3vs1 = 1.27, 95% CI: 1.11-1.44). A nonlinear, reverse L-shaped relationship was observed, with RA risk rising significantly when NPAR exceeded 13.6 (Pnon-linearity = 0.004). Subgroup analyses confirmed consistency across populations. NPAR demonstrates a superior predictive capability for RA risk when compared to other established markers, including Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), Platelet-to-Lymphocyte Ratio (PLR), Monocyteto-Lymphocyte Ratio (MLR), and Neutrophil-to-Lymphocyte Ratio (NLR).Conclusion Overall, our study demonstrates a significant positive association between NPAR and RA prevalence in U.S. adults, particularly when NPAR levels exceeded 13.6.Our findings underscore the critical role of immune-nutritional interactions in RA pathogenesis. However, owing to the cross-sectional design, prospective longitudinal investigations are warranted to establish causality and elucidate underlying biological mechanisms.
Keywords: Rheumatoid arthritis, neutrophil-percentage-to-albumin ratio, risk factor, Cross-sectional study, predictive model
Received: 19 Mar 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Liu, Zhang, He, An, Xu, Zhang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Di Liu, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
Sen Shu Zhang, Hunan University of Medicine, Huaihua, 418000, Hunan Province, China
Ruoyan Cao, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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