Neutrophil extracellular traps in immune-mediated glomerulonephritis.

Abstract: Introduction: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory systemic disease with a complex pathogenesis. Either the adaptative and the innate immunity contribute to the disease. In particular NETosis has a fundamental role but it has not yet been fully explored. Aim of the study The aim of this monocentric study was to understand the role of NETosis in SLE with renal involvement, through clinical, serological, and activity assessment of NETs both at the plasma level (NET remnants) and at the tissue level (NET score in the kidney). We also compared the SLE data with other primary and secondary glomerulonephritis. Results Thirty-tree patients affected by Lupus Nephritis (LN) underwent kidney biopsy according to clinical indication. We compared the data collected with 28 glomerulonephritis (12 IgA nephropathy, 3 ANCA vasculitis, 4 Membranous nephropathy, 4 Sjogren syndrome, 4 podocitopathy, 1 amyloidosis AL). We devised a new version of the assay for detection of NET remntans using as capture antibody the monoclonal anti alpha enolase 276/3. We found that NET remnants were correlated with anti-C1q antibodies and C4 but not with anti-dsDNA, C3 or proteinuria or ECLAM score in SLE patients. Levels of C5bC9 complexes was correlated with anti-C1q antibodies. Anti-C1q were negatively correlated with C3 level (p=0.015) and positively with anti-DNA (p= 0.011). Anti-dsDNA were highly correlated with the ECLAM score (p= 0.003) and negatively with C3. SLE patients have a high NET score in the tissue (1.57±0.93), and surprisingly it was significantly high also in IgA N if compared with all other nephritic patients (p=0.005). the NET score was directly related with C3 level (p=0.036) Conclusion: Our study demonstrated a role of NETosis in the pathogenesis of damage in lupus nephritis, correlated with disease activity and a hitherto unknown role of NETosis in primary IgA nephropathy.