Abstract |
NETs constitute a network of DNA and proteins released by neutrophils in response to infectious and immunologic triggers. NET proteins are recognized as autoantigens in ANCA vasculitis; limited knowledge is available in other autoimmune pathologies. The composition of NETs produced ex vivo by resting and Phorbol-myristate acetate (PMA) stimulated neutrophils was analyzed by high-throughput Fusion Orbitrap technology in 16 patients with Systemic Lupus Erythematosus/ Lupus nephritis (9 SLE/7 LN) and in 11 controls. Seven-hundred proteins were characterized and specific fingerprints discriminated LN from SLE. We focused on methyl-oxidized αenolase ( methionine sulfoxide 93) that was markedly increased in NETs from LN and was localized in NET filaments in tight connection and outlying DNA. The isotype of anti-αenolase antibodies was IgG2 in LN and IgG4 in other autoimmune glomerulonephritis (Membranous Nephropathy, MN); serum anti-αenolase IgG2 were higher in LN than in SLE and absent in MN. The same IgG2 antibodies recognized 5 epitopes of the protein one containing methionine sulphoxide 93. In conclusion, specific NET protein fingerprints characterize different subsets of SLE; methyl-oxidized αenolase is over-expressed in LN. Circulating anti-αenolase IgG2 recognize the oxidized epitope and are high in serum of LN patients. Post-translational modified NET proteins contribute to autoimmunity in patients with LN.
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Authors | Maurizio Bruschi, Andrea Petretto, Laura Santucci, Augusto Vaglio, Federico Pratesi, Paola Migliorini, Roberta Bertelli, Chiara Lavarello, Martina Bartolucci, Giovanni Candiano, Marco Prunotto, Gian Marco Ghiggeri |
Journal | Scientific reports
(Sci Rep)
Vol. 9
Issue 1
Pg. 7934
(05 28 2019)
ISSN: 2045-2322 [Electronic] England |
PMID | 31138830
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Autoantibodies
- Biomarkers, Tumor
- DNA-Binding Proteins
- Tumor Suppressor Proteins
- Methionine
- ENO1 protein, human
- Phosphopyruvate Hydratase
- methionine sulfoxide
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Topics |
- Adolescent
- Adult
- Aged
- Autoantibodies
(blood, immunology)
- Biomarkers, Tumor
(analysis, immunology)
- Child
- Child, Preschool
- DNA-Binding Proteins
(analysis, immunology)
- Extracellular Traps
(chemistry, immunology)
- Glomerulonephritis, Membranous
(blood, immunology, pathology)
- Humans
- Lupus Nephritis
(blood, immunology, pathology)
- Methionine
(analogs & derivatives, analysis, immunology)
- Middle Aged
- Models, Molecular
- Oxidation-Reduction
- Phosphopyruvate Hydratase
(analysis, immunology)
- Protein Interaction Maps
- Protein Processing, Post-Translational
- Tumor Suppressor Proteins
(analysis, immunology)
- Young Adult
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