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Open Access Research article

Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus

Jonatan Leffler1, Birgitta Gullstrand2, Andreas Jönsen3, Jan-Åke Nilsson3, Myriam Martin1, Anna M Blom1* and Anders A Bengtsson3

Author Affiliations

1 Lund University, Department of Laboratory Medicine Malmö, Section of Medical Protein Chemistry, Inga Marie Nilssons gata 53 floor 4, 205 02 Malmö, Sweden

2 Lund University, Department of Laboratory Medicine Lund, Section of MIG, Sölvegatan 23, 223 62 Lund, Sweden

3 Lund University, Department of Clinical Sciences, Section of Rheumatology, Kioskgatan 3, 221 85 Lund, Sweden

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Arthritis Research & Therapy 2013, 15:R84  doi:10.1186/ar4264

Published: 14 August 2013

Abstract

Introduction

The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.

Methods

Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was determined and associated with clinical parameters occurring before and at the time of sampling, as well as after sampling by using conditional logistic regression.

Results

As many as 41% of all patients in the study showed decreased ability to degrade NETs at least once, but with a median of 20% of all time points. Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased by four to five times compared to normal.

Conclusions

Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis. Potential therapeutics restoring the ability to degrade NETs could be beneficial for certain patients with SLE.

Keywords:
Systemic lupus erythematosus; neutrophil extracellular traps; degradation; glomerulonephritis; prospective study