Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93)

被引：61

作者：

Bruschi, Maurizio ^{[1
]}

Petretto, Andrea ^{[2
]}

Santucci, Laura ^{[1
]}

Vaglio, Augusto ^{[3
,4
]}

Pratesi, Federico ^{[5
]}

Migliorini, Paola ^{[5
]}

Bertelli, Roberta ^{[1
]}

Lavarello, Chiara ^{[2
]}

Bartolucci, Martina ^{[2
]}

Candiano, Giovanni ^{[1
]}

Prunotto, Marco ^{[6
]}

Ghiggeri, Gian Marco ^{[1
,7
]}

机构：

[1] IRCCS Ist Giannina Gaslini, Lab Mol Nephrol, Genoa, Italy

[2] IRCCS Ist Giannina Gaslini, Core Facil Prote Lab, Genoa, Italy

[3] Univ Firenze, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy

[4] Meyer Childrens Hosp, Florence, Italy

[5] Univ Pisa, Dept Clin & Expt Med, Clin Immunol Unit, Pisa, Italy

[6] Univ Geneva, Sch Pharmaceut Sci, Geneva, Switzerland

[7] IRCCS Ist Giannina Gaslini, Sci Inst Res & Hlth Care IRCCS, Div Nephrol Dialysis & Transplantat, Genoa, Italy

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

GLOMERULAR AUTOIMMUNE MULTICOMPONENTS; NETTING NEUTROPHILS; NADPH OXIDASE; ROC PLOTS; ANTIGEN; NETOSIS; MYELOPEROXIDASE; INFLAMMATION; ACTIVATION; BIOMARKERS;

D O I：

10.1038/s41598-019-44379-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alpha enolase (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-alpha enolase antibodies was IgG2 in LN and IgG4 in other autoimmune glomerulonephritis (Membranous Nephropathy, MN); serum anti-alpha enolase 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 alpha enolase is over-expressed in LN. Circulating anti-alpha enolase 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.

引用

页数：13

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