Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis

Bruschi, Maurizio; Bonanni, Alice; Petretto, Andrea; Vaglio, Augusto; Pratesi, Federico; Santucci, Laura; Migliorini, Paola; Bertelli, Roberta; Galetti, Mauro; Belletti, Silvana; Cavagna, Lorenzo; Moroni, Gabriella; Franceschini, Franco; Fredi, Micaela; Pazzola, Giulia; Allegri, Landino; Sinico, Renato Alberto; Pesce, Giampaola; Bagnasco, Marcello; Manfredi, Angelo A.; Ramirez, Giuseppe A.; Ramoino, Paola; Bianchini, Paolo; Puppo, Francesco; Pupo, Francesca; Negrini, Simone; Mattana, Federico; Emmi, Giacomo; Garibotto, Giacomo; Santoro, Domenico; Scolari, Francesco; Ravelli, Angelo; Tincani, Anǵela; Cravedi, Paolo; Volpi, Stefano; Candiano, Giovanni; Ghiggeri, Gian Marco

doi:10.3899/jrheum.181232

Cited by 94 publications

(87 citation statements)

References 37 publications

(44 reference statements)

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“…None of these control subjects carried either c.290_291delCA (p.Thr97Ilefs ∗ 2) or c.563G>C (p.Gln188Arg). JIA is the most common pediatric rheumatic disease and includes all forms of arthritis that begin before adulthood and are of unknown origin, which share some features, such as uveitis and presence of autoantibodies, 36 with HUVS. Therefore, we enrolled patients with JIA as pediatric autoimmune disease control subjects.…”

Section: Methodsmentioning

confidence: 99%

Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction

Chan

Serpas

et al. 2020

The American Journal of Human Genetics

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Summary Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset and anti- ds DNA reactivity. In this study, we found that human patients with DNASE1L3 disease-associated gene variations showed aberrations in size and a reduction of a “CC” end motif of plasma DNA. Furthermore, we demonstrated that DNA from DNASE1L3-digested cell nuclei showed a median length of 153 bp with CC motif frequencies resembling plasma DNA from healthy individuals. Adeno-associated virus-based transduction of Dnase1l3 into Dnase1l3 -deficient mice restored the end motif profiles to those seen in the plasma DNA of wild-type mice. Our findings demonstrate that DNASE1L3 is an important player in the fragmentation of plasma DNA, which appears to act in a cell-extrinsic manner to regulate plasma DNA size and motif frequency.

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Section: Methodsmentioning

confidence: 99%

Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction

Chan

Serpas

et al. 2020

The American Journal of Human Genetics

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“…There is a possible production of autoantibodies against nucleic acids released by neutrophils undergoing NETosis [ 19 , 68 ] with the generated immune complexes representing a source of self-antigens that enhance the autoimmune and inflammatory process. This in turn results in more injury and inflammation [ 20 , 69 ].…”

Section: Effects Of Netsmentioning

confidence: 99%

A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics

Mutua

Gershwin

2020

Clinic Rev Allerg Immunol

309

248

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Activated neutrophils release neutrophil extracellular traps (NETs) in response to a variety of stimuli. NETosis is driven by protein-arginine deiminase type 4, with the release of intracellular granule components that function by capturing and destroying microbes, including viral, fungal, bacterial, and protozoal pathogens. The positive effects of pathogen control are countered by pro-inflammatory effects as demonstrated in a variety of diseases. Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response. NETs can play a role in enhancement of the inflammation seen in autoimmune diseases including psoriasis, rheumatoid arthritis, and systemic lupus erythematosis. In addition, autoinflammatory diseases such as gout have been associated with NETosis. Inhibition of NETs may decrease the severity of many diseases improving survival. Herein, we describe NETosis in different diseases focusing on the detrimental effect of NETs and outline possible therapeutics that can be used to mitigate netosis. There is a need for more studies and clinical trials on these and other compounds that could prevent or destroy NETs, thereby decreasing damage to patients.

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“…DNase II is a major lysosomal endonuclease that plays a pivotal role in the degradation of exogenous DNA encountered by endocytosis. Deoxyribonuclease 1 like 3 (DNase1L3) is homologous with DNase I and is presumed to play a role in clearance of neutrophil extracellular traps (NETs) [122].…”

Section: Deoxyribonuclease Deficienciesmentioning

confidence: 99%

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

Demirkaya

Şahin

Romano

et al. 2020

JCM

100

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Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.

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Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis

Cited by 94 publications

References 37 publications

Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction

Plasma DNA Profile Associated with DNASE1L3 Gene Mutations: Clinical Observations, Relationships to Nuclease Substrate Preference, and In Vivo Correction

A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics

New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

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