RT Journal Article SR Electronic T1 Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.181232 DO 10.3899/jrheum.181232 A1 Maurizio Bruschi A1 Alice Bonanni A1 Andrea Petretto A1 Augusto Vaglio A1 Federico Pratesi A1 Laura Santucci A1 Paola Migliorini A1 Roberta Bertelli A1 Maricla Galetti A1 Silvana Belletti A1 Lorenzo Cavagna A1 Gabriella Moroni A1 Franco Franceschini A1 Micaela Fredi A1 Giulia Pazzola A1 Landino Allegri A1 Renato Alberto Sinico A1 Giampaola Pesce A1 Marcello Bagnasco A1 Angelo Manfredi A1 Giuseppe A. Ramirez A1 Paola Ramoino A1 Paolo Bianchini A1 Francesco Puppo A1 Francesca Pupo A1 Simone Negrini A1 Federico Mattana A1 Giacomo Emmi A1 Giacomo Garibotto A1 Domenico Santoro A1 Francesco Scolari A1 Angelo Ravelli A1 Angela Tincani A1 Paolo Cravedi A1 Stefano Volpi A1 Giovanni Candiano A1 Gian Marco Ghiggeri YR 2019 UL http://www.jrheum.org/content/early/2019/11/25/jrheum.181232.abstract AB Objective Neutrophil extracellular traps (NET) expose modified antigens for autoantibodies in vasculitis. Little is known about levels and removal pathways of NET in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NET removal in large subsets of patients with incident SLE (iSLE), some of whom had new-onset nephritis. Methods Serum levels of NET (ELISA), DNase1/DNase1L3 (ELISA), and DNase activity (functional assay) were determined in 216 patients with iSLE [103 had incident LN (iLN)], in 50 patients with other primary glomerulonephritis, and in healthy controls. Ex vivo NET production by neutrophils purified from a random selection of patients was quantified as elastase/DNA release and by immunofluorescence techniques. Results Serum NET levels were very high in iSLE/iLN compared to all groups of controls and correlated with anti-dsDNA, C3–C4, and proteinuria; iLN had the highest levels. DNase activity was decreased in iLN compared to SLE (20% had one-half DNase activity) despite similar serum levels of DNase1/DNase1L3. In these cases, pretreatment of serum with protein A restored DNase efficiency; 1 patient was homozygous for a c.289_290delAC variant of DNASE1L3. Ex vivo NET production by neutrophils purified from LN, SLE, and normal controls was similar in all cases. Conclusion Patients with iLN have increased circulating NET and reduced DNase activity, the latter being explained by the presence of inhibitory substances in circulation and/or by rare DNase1L3 mutations. Accumulation of NET derives from a multifactorial mechanism, and is associated and may contribute to disease severity in SLE, in particular to renal lesions. (Clinical trial registration: The Zeus study was registered at ClinicalTrials.gov, study number NCT02403115).