The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus

Chokchai Thanadetsuntorn,Kenneth Hodge,Chavachol Setthaudom,Prapaporn Pisitkun,Pintip Ngamjanyaporn,Nisara Saengpiya

doi:10.1038/s41598-018-20947-4

Chokchai Thanadetsuntorn, Kenneth Hodge + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-20947-4

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Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99–26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16–8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.

Highlights

Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting all organ systems leading to inflammation and tissue damage[1]
This study aimed to investigate whether serum levels of IL-6 and circulating immune complexes (CIC) correlated with SLE disease activity achieved by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) and modified SLEDAI-2K
The active SLE group had a statistically significant higher erythrocyte sedimentation rate (ESR) and urine protein to creatinine ratio, but lower absolute lymphocyte counts compared with patients in the inactive SLE group

Summary

Introduction

Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting all organ systems leading to inflammation and tissue damage[1]. The key cytokine involved in SLE pathogenesis is interferon alpha (IFN- α) which leads to upregulation of several inflammatory proteins[6]. Another study showed higher levels of IL-6 in SLE with hematological manifestation, but did not correlate with other individual organ and systemic disease activity[14]. Elevated serum levels of circulating immune complexes (CIC) have long been described in lupus, which leads to organ inflammation and damage by immune complex deposition. Few studies show the detection of CIC is specific for SLE, and correlates with disease activity and deposits in the kidney of lupus nephritis patients[16,17]. This study aimed to investigate whether serum levels of IL-6 and CIC correlated with SLE disease activity achieved by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) and modified SLEDAI-2K. The analysis of biomarker models would be compared to reveal the model that provides the best prediction for SLE disease activity

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