{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:11:26Z","timestamp":1790856686496,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["PNRR M6C2"],"award-info":[{"award-number":["PNRR M6C2"]}]},{"name":"European Union","award":["PNRR M6C2"],"award-info":[{"award-number":["PNRR M6C2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The complement cascade and Neutrophil Extracellular Traps (NETs) represent fundamental tools in protecting the host from foreign pathogens. Complement components and relative fragments, classically assigned to the innate immunity, represent a key link with the humoral immune response. NETs are a crucial component of the innate immune response, consisting of chromatin release from activated neutrophils. These web-like structures facilitate pathogen entrapment and elimination through proteolytic degradation and antimicrobial effectors. Previous findings suggested complement components and NETs have a significant role in the pathogenesis of several diseases characterized by inflammation, such as autoimmune and infectious diseases. However, the crosstalk between NETs and the complement cascade has only recently been investigated, and several aspects still need to be fully clarified. Recent evidence seems to suggest a bidirectional link between the complement cascade and NETosis. We here present the interaction between complement components and NETs in specific autoimmune diseases that mostly affect the kidney, such as systemic lupus erythematosus, Antineutrophilic Cytoplasmic Antibody (ANCA)-associated vasculitis and antiphospholipid syndrome. The mechanisms reported here may represent specific targets for the development of possible therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26062789","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"2789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Crosstalk Between NETs and the Complement Cascade: An Overview in Nephrological Autoimmune Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-7584","authenticated-orcid":false,"given":"Xhuliana","family":"Kajana","sequence":"first","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-3001","authenticated-orcid":false,"given":"Gianluca","family":"Caridi","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Bruschi","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-4308","authenticated-orcid":false,"given":"Sonia","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Lugani","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Marco","family":"Ghiggeri","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"La Porta","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Mortari","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico E.","family":"Verrina","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-5326","authenticated-orcid":false,"given":"Andrea","family":"Angeletti","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8563-8351","authenticated-orcid":false,"given":"Carolina","family":"Bigatti","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, 16145 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement. First of two parts","volume":"344","author":"Walport","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJM200104123441506","article-title":"Complement. Second of two parts","volume":"344","author":"Walport","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1025861","DOI":"10.3389\/fimmu.2022.1025861","article-title":"Bibliometric and visual analysis of neutrophil extracellular traps from 2004 to 2022","volume":"13","author":"Wan","year":"2022","journal-title":"Front Immunol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.autrev.2015.03.002","article-title":"Neutrophil extracellular traps and their role in the development of chronic inflammation and autoimmunity","volume":"14","author":"Pinegin","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109448","DOI":"10.1016\/j.intimp.2022.109448","article-title":"Protein kinase C isoforms mediate the formation of neutrophil extracellular traps","volume":"114","author":"Vorobjeva","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11037","DOI":"10.1038\/ncomms11037","article-title":"Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis","volume":"7","author":"Guglietta","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Karpati, E., Kremlitzka, M., Sandor, N., Hajnal, D., Schneider, A.E., and Jozsi, M. (2021). Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.660852"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molimm.2016.02.011","article-title":"Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps","volume":"72","author":"Schneider","year":"2016","journal-title":"Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jre.12284","article-title":"Influence of complement on neutrophil extracellular trap release induced by bacteria","volume":"51","author":"Palmer","year":"2016","journal-title":"J. Periodontal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F1308","DOI":"10.1152\/ajprenal.00645.2014","article-title":"Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin","volume":"310","author":"Dixon","year":"2016","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/eji.201646703","article-title":"Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-gamma","volume":"47","author":"Dixon","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000356980","article-title":"Myeloperoxidase directs properdin-mediated complement activation","volume":"6","author":"Dixon","year":"2014","journal-title":"J. Innate Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0171-2985(96)80050-7","article-title":"Complement activation by myeloperoxidase products released from stimulated human polymorphonuclear leukocytes","volume":"195","author":"Vogt","year":"1996","journal-title":"Immunobiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41423-018-0024-0","article-title":"NETosis, complement, and coagulation: A triangular relationship","volume":"16","author":"Boelens","year":"2019","journal-title":"Cell Mol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"921","DOI":"10.4049\/jimmunol.147.3.921","article-title":"Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G","volume":"147","author":"Maison","year":"1991","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/cei.12654","article-title":"Neutrophil extracellular traps can activate alternative complement pathways","volume":"181","author":"Wang","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.4049\/jimmunol.1102404","article-title":"Neutrophil extracellular traps that are not degraded in systemic lupus erythematosus activate complement exacerbating the disease","volume":"188","author":"Leffler","year":"2012","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yuen, J., Pluthero, F.G., Douda, D.N., Riedl, M., Cherry, A., Ulanova, M., Kahr, W.H., Palaniyar, N., and Licht, C. (2016). NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00137"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Halder, L.D., Abdelfatah, M.A., Jo, E.A., Jacobsen, I.D., Westermann, M., Beyersdorf, N., Lorkowski, S., Zipfel, P.F., and Skerka, C. (2016). Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00671"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/ard-2023-224762","article-title":"EULAR recommendations for the management of systemic lupus erythematosus: 2023 update","volume":"83","author":"Fanouriakis","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) (2021). KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int, 100, S1\u2013S276."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/s41590-019-0466-2","article-title":"Interferon target-gene expression and epigenomic signatures in health and disease","volume":"20","author":"Barrat","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Herrada, A.A., Escobedo, N., Iruretagoyena, M., Valenzuela, R.A., Burgos, P.I., Cuitino, L., and Llanos, C. (2019). Innate Immune Cells\u2019 Contribution to Systemic Lupus Erythematosus. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00772"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.kint.2022.02.031","article-title":"Type I interferon-related kidney disorders","volume":"101","author":"Lodi","year":"2022","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41577-022-00787-0","article-title":"Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases","volume":"23","author":"Wigerblad","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1191\/9612332lu155oa","article-title":"Baseline characteristics of a multiethnic lupus cohort: PROFILE","volume":"11","author":"Alarcon","year":"2002","journal-title":"Lupus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/art.39594","article-title":"Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971\u20132015: A Systematic Review and Bayesian Meta-Analysis","volume":"68","author":"Tektonidou","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1681\/ASN.2009101093","article-title":"Recurrence of lupus nephritis after kidney transplantation","volume":"21","author":"Contreras","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bertelli, R., Schena, F., Antonini, F., Reverberi, D., Signa, S., Pedemonte, N., Consolaro, A., Gattorno, M., Negrini, S., and Pupo, F. (2021). Neutrophil Extracellular Traps in Systemic Lupus Erythematosus Stimulate IgG2 Production From B Lymphocytes. Front. Med., 8.","DOI":"10.3389\/fmed.2021.635436"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jaut.2015.08.018","article-title":"The responses of macrophages in interaction with neutrophils that undergo NETosis","volume":"67","author":"Nakazawa","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cca.2016.11.006","article-title":"Post-translational modified proteins are biomarkers of autoimmune-processes: NETosis and the inflammatory-autoimmunity connection","volume":"464","author":"Bruschi","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bruschi, M., Petretto, A., Santucci, L., Vaglio, A., Pratesi, F., Migliorini, P., Bertelli, R., Lavarello, C., Bartolucci, M., and Candiano, G. (2019). Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized alphaenolase (methionine sulfoxide 93). Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44379-w"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bruschi, M., Moroni, G., Sinico, R.A., Franceschini, F., Fredi, M., Vaglio, A., Cavagna, L., Petretto, A., Pratesi, F., and Migliorini, P. (2021). Neutrophil Extracellular Traps in the Autoimmunity Context. Front. Med., 8.","DOI":"10.3389\/fmed.2021.614829"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4172\/2155-9899.1000139","article-title":"Neutrophil Extracellular Traps and Systemic Lupus Erythematosus","volume":"4","author":"Yu","year":"2013","journal-title":"J. Clin. Cell Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4049\/jimmunol.1202388","article-title":"Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages","volume":"190","author":"Kahlenberg","year":"2013","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3899\/jrheum.181232","article-title":"Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis","volume":"47","author":"Bruschi","year":"2020","journal-title":"J. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, W., Su, J., Yan, M., Pan, J., and Zhang, X. (2023). Neutrophil extracellular traps in autoimmune diseases: Analysis of the knowledge map. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1095421"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Takagi, H., Arimura, K., Uto, T., Fukaya, T., Nakamura, T., Choijookhuu, N., Hishikawa, Y., and Sato, K. (2016). Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation. Sci. Rep., 6.","DOI":"10.1038\/srep24477"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Demkow, U. (2023). Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054896"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1002\/art.41460","article-title":"Anti-Neutrophil Extracellular Trap Antibodies and Impaired Neutrophil Extracellular Trap Degradation in Antiphospholipid Syndrome","volume":"72","author":"Zuo","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Reshetnyak, T., and Nurbaeva, K. (2023). The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713581"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2478\/rir-2022-0003","article-title":"Contribution of Impaired DNASE1L3 Activity to Anti-DNA Autoantibody Production in Systemic Lupus Erythematosus","volume":"3","author":"Mathapathi","year":"2022","journal-title":"Rheumatol. Immunol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00439-018-01966-7","article-title":"Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus","volume":"138","author":"Almlof","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/91070","article-title":"Mutation of DNASE1 in people with systemic lupus erythematosus","volume":"28","author":"Yasutomo","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104262","DOI":"10.1016\/j.ejmg.2021.104262","article-title":"Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis","volume":"64","author":"Balci","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e20201138","DOI":"10.1084\/jem.20201138","article-title":"Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus","volume":"218","author":"Hartl","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood-2016-06-722298","article-title":"In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps","volume":"129","author":"Noubouossie","year":"2017","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jaut.2019.01.003","article-title":"Neutrophil extracellular traps exert both pro- and anti-inflammatory actions in rheumatoid arthritis that are modulated by C1q and LL-37","volume":"98","author":"Ribon","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.autrev.2016.03.007","article-title":"Pathogenesis of ANCA-associated vasculitis: An update","volume":"15","author":"Jarrot","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shiratori-Aso, S., and Nakazawa, D. (2023). The involvement of NETs in ANCA-associated vasculitis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1261151"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Huang, S.U., and O\u2019Sullivan, K.M. (2022). The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202203.0021.v1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1136\/annrheumdis-2013-203430","article-title":"Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease","volume":"73","author":"Kambas","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nakazawa, D., Tomaru, U., Yamamoto, C., Jodo, S., and Ishizu, A. (2012). Abundant neutrophil extracellular traps in thrombus of patient with microscopic polyangiitis. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00333"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1002\/1878-0261.12787","article-title":"AAV-mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response","volume":"14","author":"Xia","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Patriarcheas, V., Tsamos, G., Vasdeki, D., Kotteas, E., Kollias, A., Nikas, D., Kaiafa, G., and Dimakakos, E. (2025). Antiphospholipid Syndrome: A Comprehensive Clinical Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14030733"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1093\/rheumatology\/kew196","article-title":"Autoantibodies against a complement component 1 q subcomponent contribute to complement activation and recurrent thrombosis\/pregnancy morbidity in anti-phospholipid syndrome","volume":"55","author":"Oku","year":"2016","journal-title":"Rheumatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12959-022-00384-0","article-title":"Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis","volume":"20","author":"Chen","year":"2022","journal-title":"Thromb. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00281-022-00916-w","article-title":"Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome","volume":"44","author":"Knight","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1182\/bloodadvances.2020003093","article-title":"Inhibition of NADPH oxidase blocks NETosis and reduces thrombosis in heparin-induced thrombocytopenia","volume":"5","author":"Leung","year":"2021","journal-title":"Blood Adv."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bulnes, J.F., Gonzalez, L., Velasquez, L., Orellana, M.P., Venturelli, P.M., and Martinez, G. (2024). Role of inflammation and evidence for the use of colchicine in patients with acute coronary syndrome. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1356023"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1161\/CIRCRESAHA.114.303312","article-title":"Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis","volume":"114","author":"Knight","year":"2014","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.4049\/jimmunol.1700639","article-title":"PAD4 Deficiency Leads to Decreased Organ Dysfunction and Improved Survival in a Dual Insult Model of Hemorrhagic Shock and Sepsis","volume":"200","author":"Biron","year":"2018","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"174623","DOI":"10.1016\/j.ejphar.2021.174623","article-title":"Inhibition of PAD4-mediated NET formation by cl-amidine prevents diabetes development in nonobese diabetic mice","volume":"916","author":"Shen","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000448808","article-title":"Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model","volume":"9","author":"Biron","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sondo, E., Bertelli, R., Pesce, E., Ghiggeri, G.M., and Pedemonte, N. (2019). High-Content Screening Identifies Vanilloids as a Novel Class of Inhibitors of NET Formation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00963"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-024-01933-x","article-title":"Neutrophil extracellular traps in homeostasis and disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fan, X., Shu, P., Wang, Y., Ji, N., and Zhang, D. (2023). Interactions between neutrophils and T-helper 17 cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1279837"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41423-024-01158-6","article-title":"Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease","volume":"21","author":"Wang","year":"2024","journal-title":"Cell Mol. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1164\/ajrccm.163.5.2005002","article-title":"Improved activity of an actin-resistant DNase I variant on the cystic fibrosis airway secretions","volume":"163","author":"Zahm","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3233\/ADR-190100","article-title":"Mining Clinical Case Reports to Identify New Lines of Investigation in Alzheimer\u2019s Disease: The Curious Case of DNase I","volume":"3","author":"Smalheiser","year":"2019","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/pro.5560020501","article-title":"The curious case of protein splicing: Mechanistic insights suggested by protein semisynthesis","volume":"2","author":"Wallace","year":"1993","journal-title":"Protein Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/ar1936","article-title":"The in vivo expression of actin\/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus","volume":"8","author":"Manderson","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1191\/096120399678847380","article-title":"Recombinant human Dnase I (rhDNase) in patients with lupus nephritis","volume":"8","author":"Davis","year":"1999","journal-title":"Lupus"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s12016-021-08898-7","article-title":"The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies","volume":"63","author":"Wang","year":"2022","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Marinho, A., Delgado Alves, J., Fortuna, J., Faria, R., Almeida, I., Alves, G., Araujo Correia, J., Campar, A., Brandao, M., and Crespo, J. (2023). Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjogren\u2019s syndrome: Evidence- and practice-based guidance. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1117699"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nbt1344","article-title":"Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria","volume":"25","author":"Rother","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1056\/NEJMoa1208981","article-title":"Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome","volume":"368","author":"Legendre","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_79","first-page":"2286","article-title":"Eculizumab as rescue therapy in severe resistant lupus nephritis","volume":"54","author":"Pickering","year":"2015","journal-title":"Rheumatology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.2169\/internalmedicine.0228-17","article-title":"A Rare Case of Lupus Nephritis Presenting as Thrombotic Microangiopathy with Diffuse Pseudotubulization Possibly Caused by Atypical Hemolytic Uremic Syndrome","volume":"57","author":"Ono","year":"2018","journal-title":"Intern. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00296-017-3686-5","article-title":"Expanding the therapeutic options for renal involvement in lupus: Eculizumab, available evidence","volume":"37","author":"Sciascia","year":"2017","journal-title":"Rheumatol. Int."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wright, R.D., Bannerman, F., Beresford, M.W., and Oni, L. (2020). A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic microangiopathy. BMC Nephrol., 21.","DOI":"10.1186\/s12882-020-01888-5"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1681\/ASN.2016111179","article-title":"Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis","volume":"28","author":"Jayne","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_84","first-page":"782","article-title":"Key considerations for modelling the long-term costs and benefits of treatments for ANCA-associated vasculitis","volume":"42","author":"Berdunov","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"101618","DOI":"10.1016\/j.smim.2022.101618","article-title":"Discovering C3 targeting therapies for paroxysmal nocturnal hemoglobinuria: Achievements and pitfalls","volume":"59","author":"Risitano","year":"2022","journal-title":"Semin. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"D\u2019Alessandro, M., Conticini, E., Bergantini, L., Cameli, P., Cantarini, L., Frediani, B., and Bargagli, E. (2022). Neutrophil Extracellular Traps in ANCA-Associated Vasculitis and Interstitial Lung Disease: A Scoping Review. Life, 12.","DOI":"10.3390\/life12020317"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"O\u2019Sullivan, K.M., and Holdsworth, S.R. (2021). Neutrophil Extracellular Traps: A Potential Therapeutic Target in MPO-ANCA Associated Vasculitis?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.635188"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e01755-17","DOI":"10.1128\/mBio.01755-17","article-title":"Complement C5a Receptor 1 Exacerbates the Pathophysiology of N. meningitidis Sepsis and Is a Potential Target for Disease Treatment","volume":"9","author":"Herrmann","year":"2018","journal-title":"mBio"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/s41419-021-04294-3","article-title":"The emerging roles of neutrophil extracellular traps in wound healing","volume":"12","author":"Zhu","year":"2021","journal-title":"Cell Death Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:54Z","timestamp":1760029014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":89,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062789"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062789","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,20]]}}}