Serum Interleukin-26 Is a New Biomarker for Disease Activity Assessment in Systemic Lupus Erythematosus.

Benoit Brilland,Vincent Larochette,Patrick Saulnier,Pascale Jeannin,Maxime Bach-Bunner,Jean-François Augusto,Etienne Foucher,Cristina Belizna,Marc Plaisance,Christopher Nunes Gomes,Nathalie Costedoat-Chalumeau,Pascale Ghillani,Yves Delneste

doi:10.3389/fimmu.2021.663192

Abstract

ObjectiveInterleukin-26 (IL-26) has a unique ability to activate innate immune cells due to its binding to circulating double-stranded DNA. High levels of IL-26 have been reported in patients with chronic inflammation. We aimed to investigate IL-26 levels in patients with systemic lupus erythematosus (SLE).MethodsIL-26 serum levels were quantified by ELISA for 47 healthy controls and 109 SLE patients previously enrolled in the PLUS study. Performance of IL-26 levels and classical markers (autoantibodies or complement consumption) to identify an active SLE disease (SLE disease activity index (SLEDAI) score > 4) were compared.ResultsIL-26 levels were significantly higher in SLE patients than in controls (4.04 ± 11.66 and 0.74 ± 2.02 ng/mL; p = 0.005). IL-26 levels were also significantly higher in patients with active disease than those with inactive disease (33.08 ± 21.06 vs 1.10 ± 3.80 ng/mL, p < 0.0001). IL-26 levels correlated with SLEDAI score and the urine protein to creatinine ratio (uPCR) (p < 0.001). Patients with high IL-26 levels had higher SLEDAI score, anti-DNA antibodies levels, and uPCR (p < 0.05). They presented more frequently with C3 or C4 complement consumption. Lastly, IL-26 showed stronger performance than classical markers (complement consumption or autoantibodies) for active disease identification.ConclusionsOur results suggest that, in addition to classical SLE serological markers, the measurement of IL-26 levels may be a useful biomarker for active disease identification in SLE patients.

Highlights

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with the presence of autoantibodies and the formation of immune complexes that cause tissue damage
The activation of antigenpresenting cells (APCs), which is required to initiate antigen-specific immune responses, is induced via intracellular DNA sensors, including TLR9 [2]. This process induces the production of type I interferons (IFN-I) by plasmacytoid dendritic cells, which play a central role in the pathogenesis of lupus [3]
We report that the levels of IL-26 are higher in SLE patients than healthy subjects and show a significant correlation with disease activity

Summary

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with the presence of autoantibodies and the formation of immune complexes that cause tissue damage (mainly targeting the skin, kidneys, and brain). Autoantibodies directed against double-stranded (ds) DNA play a key role in the initiation and maintenance of inflammatory lesions in SLE [1]. Such autoantibodies were the first identified DNA shuttling molecules allowing extracellular DNA (i.e. released by dying cells) to be internalized via the FcgR and processed by antigenpresenting cells (APCs). The activation of APCs, which is required to initiate antigen-specific immune responses, is induced via intracellular DNA sensors, including TLR9 [2] This process induces the production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs), which play a central role in the pathogenesis of lupus [3]. Anti-DNA Abs and anti-microbial peptides are not always found in SLE patients, suggesting the existence of other DNA shuttling molecules

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