Investigating the presence of neutrophil extracellular traps in cutaneous lesions of different subtypes of lupus erythematosus

Abstract

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin-fixed paraffin-embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR-3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.

Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light

“…In SLE, a neutrophil gene signature is a strong predictor of active disease including LN and cutaneous lupus [15][16][17] . Neutrophils are found in cutaneous lesions [10][11][12] as well as kidney biopsy specimens 13,14 of SLE patients and their inflammatory properties have been attributed to NET formation 14,21 . This process includes increased production of ROS 19,82 , mitochondrial DNA release 19 , as well as release and induction of inflammatory proteins such as s100A9 83 , IL-1b 84 , and type I interferons 19,85,86 .…”

“…Recent findings indicate that neutrophils play an important role in both local and systemic lupus disease. Neutrophils are present in the skin lesions of SLE patients [10][11][12] as well as in the kidney tissue of patients with LN 13,14 . High expression of a neutrophil gene signature is a strong predictor of active SLE, including nephritis and cutaneous flares [15][16][17] .…”

Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis

“…Some neutrophils have the ability to produce neutrophil extracellular traps (NETs), which are comprised of DNA, chromatin and various proteins. NETs have been found in various CLE subtypes including: lupus panniculitis, ACLE, DLE, and to a lesser extent, SCLE (96). Though the study by Safi et al (96) included a cohort of only 30 patients, their work indicates the presence and contribution of NETs in CLE is worth further investigation.…”

“…NETs have been found in various CLE subtypes including: lupus panniculitis, ACLE, DLE, and to a lesser extent, SCLE (96). Though the study by Safi et al (96) included a cohort of only 30 patients, their work indicates the presence and contribution of NETs in CLE is worth further investigation. A subclass of neutrophils, called low density granulocytes (LDGs), have an increased propensity for producing NETs.…”

Focus theme issue: Celebrating the ADF‐EXD partnership: A look back into the future of experimental dermatology

“…The authors suggest a multistep targeting approach as well as an individualized treatment strategy. [27][28][29][30] Subsequently, the topic of cutaneous lupus erythematosus [31][32][33] is covered by Fetter et al [32] The authors summarize current findings of the underlying pathomechanisms and highlight specific biomarkers as well as current clinical studies. [32,33] This special Focus Theme Issue celebrating the partnership of ADF with its home journal is concluded by the paper of Emmert et al, [34] who report how human 3D skin "equivalent" models have evolved over the past few years.…”