Abstract
IntroductionThe 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.MethodsSerum 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.ResultsAs 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.ConclusionsDecreased 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.
Highlights
The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE)
Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA
Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis
Summary
The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). Numerous recent reports further show involvement of NETs in SLE This spans from how NETs are more formed by neutrophils isolated from SLE patients, potentially through elevated interferon-a levels or the presence of activating antibodies in these patients to how non-degradable complexes of chromatin and antimicrobial peptides are found in SLE sera [9]. Together, this all could contribute to the tissue damage in SLE [10]. We identified a number of distinct clinical manifestations and laboratory variables that preceded the time-point of decreased NET degradation and some that appeared at the same time-point as well as after the time-point of decreased NET degradation
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