Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis

Autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, spondyloarthritis (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), are characterized by chronic immune activation and systemic inflammation. The systemic immune...

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Main Authors: Yang Wu, Yupeng Huang, Yan Wu, Jianhong Sun, Qibing Xie, Geng Yin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621209/full
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author Yang Wu
Yupeng Huang
Yan Wu
Jianhong Sun
Qibing Xie
Geng Yin
author_facet Yang Wu
Yupeng Huang
Yan Wu
Jianhong Sun
Qibing Xie
Geng Yin
author_sort Yang Wu
collection DOAJ
description Autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, spondyloarthritis (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), are characterized by chronic immune activation and systemic inflammation. The systemic immune-inflammation index (SII), computed as platelet count × neutrophil count/lymphocyte count, is a promising biomarker that reflects both inflammatory burden and immune dysregulation. In RA, elevation of SII is correlated with disease activity score, response to TNF-α inhibitors, and reduced serum Klotho levels. In AS and PsA, the SII is associated with disease activity scores, musculoskeletal imaging findings, and treatment response. In SLE, the SII tracks global activity and predicts lupus nephritis and pregnancy outcomes, while further reflecting underlying features, such as lymphopenia, neutrophil extracellular trap formation, and platelet activation. The SII is also useful in vasculitis-related diseases, including Behçet’s syndrome and Kawasaki disease. In comparison to traditional markers such as CRP and ESR, the SII provides broader immune insights than routine hematologic data. SII is influenced by non-autoimmune factors, including malignancy and infection, which are often excluded from autoimmune studies, although significant in clinical interpretation. This review summarizes the latest evidence on the SII across autoimmune conditions. It also aims to outline the key limitations and future directions, including longitudinal validation, integration with emerging indices (e.g., the systemic inflammatory response index), and its role in multimodal disease monitoring.
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spelling doaj-art-787cb43b161b4e059eef5986befee5cd2025-08-20T03:40:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16212091621209Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritisYang Wu0Yupeng Huang1Yan Wu2Jianhong Sun3Qibing Xie4Geng Yin5Department of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaOutpatient Department, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaAutoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, spondyloarthritis (SpA), including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), are characterized by chronic immune activation and systemic inflammation. The systemic immune-inflammation index (SII), computed as platelet count × neutrophil count/lymphocyte count, is a promising biomarker that reflects both inflammatory burden and immune dysregulation. In RA, elevation of SII is correlated with disease activity score, response to TNF-α inhibitors, and reduced serum Klotho levels. In AS and PsA, the SII is associated with disease activity scores, musculoskeletal imaging findings, and treatment response. In SLE, the SII tracks global activity and predicts lupus nephritis and pregnancy outcomes, while further reflecting underlying features, such as lymphopenia, neutrophil extracellular trap formation, and platelet activation. The SII is also useful in vasculitis-related diseases, including Behçet’s syndrome and Kawasaki disease. In comparison to traditional markers such as CRP and ESR, the SII provides broader immune insights than routine hematologic data. SII is influenced by non-autoimmune factors, including malignancy and infection, which are often excluded from autoimmune studies, although significant in clinical interpretation. This review summarizes the latest evidence on the SII across autoimmune conditions. It also aims to outline the key limitations and future directions, including longitudinal validation, integration with emerging indices (e.g., the systemic inflammatory response index), and its role in multimodal disease monitoring.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621209/fullsystemic immune-inflammation indexautoimmune diseasesrheumatoid arthritissystemic lupus erythematosusbiomarkers of inflammation
spellingShingle Yang Wu
Yupeng Huang
Yan Wu
Jianhong Sun
Qibing Xie
Geng Yin
Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
Frontiers in Immunology
systemic immune-inflammation index
autoimmune diseases
rheumatoid arthritis
systemic lupus erythematosus
biomarkers of inflammation
title Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
title_full Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
title_fullStr Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
title_full_unstemmed Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
title_short Systemic immune-inflammation index as a versatile biomarker in autoimmune disorders: insights from rheumatoid arthritis, lupus, and spondyloarthritis
title_sort systemic immune inflammation index as a versatile biomarker in autoimmune disorders insights from rheumatoid arthritis lupus and spondyloarthritis
topic systemic immune-inflammation index
autoimmune diseases
rheumatoid arthritis
systemic lupus erythematosus
biomarkers of inflammation
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621209/full
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