{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T17:54:12Z","timestamp":1793555652900,"version":"4.5.0"},"reference-count":190,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious cycle of inflammation and vascular damage in AAV. On the other hand, platelets have recently been recognized as essential for thrombosis and as inflammatory effectors that collaborate with neutrophils, reinforcing the generation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in those diseases. Neutrophils exhibit morphological and functional heterogeneity in AAV, reflecting the complexity of their contribution to disease pathogenesis. Since long-term immunosuppression may be related to serious infections and malignancies, there is an urgent need for reliable biomarkers of disease activity to optimize the management of AAV. This review summarizes the current understanding of the role of neutrophils and platelets in the pathogenesis of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), focusing on their crosstalk, and highlights the potential for identifying novel biomarkers relevant for predicting the disease course and its relapses.<\/jats:p>","DOI":"10.3390\/diagnostics15151905","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"1905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5556-2637","authenticated-orcid":false,"given":"Anna","family":"Drynda","sequence":"first","affiliation":[{"name":"Doctoral School of Medical Sciences and Health Sciences, Jagiellonian University Medical College, 31-530 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-1488","authenticated-orcid":false,"given":"Marcin","family":"Surmiak","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-0963","authenticated-orcid":false,"given":"Stanis\u0142awa","family":"Bazan-Socha","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Wawrzycka-Adamczyk","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Korkosz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Musia\u0142","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9786-2499","authenticated-orcid":false,"given":"Krzysztof","family":"W\u00f3jcik","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","first-page":"180","article-title":"2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Rheum. Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4283928","DOI":"10.1155\/2024\/4283928","article-title":"Clinical characteristics of EGPA patients in comparison to GPA subgroup with increased blood eosinophilia from Polvas Registry","volume":"2024","author":"Drynda","year":"2024","journal-title":"J. Immunol. Res."},{"key":"ref_3","first-page":"16187","article-title":"Association of antineutrophil cytoplasmic antibody (ANCA) specificity with the demographic and clinical characteristics of patients with ANCA-associated vasculitides","volume":"132","author":"Masiak","year":"2022","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_4","first-page":"720","article-title":"Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: A retrospective study based on POLVAS Registry","volume":"40","author":"Zdrojewski","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1053\/j.akdh.2024.08.006","article-title":"Rapidly progressive glomerulonephritis","volume":"31","author":"Koirala","year":"2024","journal-title":"Adv. Kidney Dis. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1093\/rheumatology\/keab495","article-title":"Significance of eosinophilia in granulomatosis with polyangiitis: Data from the French Vasculitis Study Group Registry","volume":"61","author":"Iudici","year":"2022","journal-title":"Rheumatology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Quan, M.V., Frankel, S.K., Maleki-Fischbach, M., and Tan, L.D. (2018). A rare case report of polyangiitis overlap syndrome: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. BMC Pulm. Med., 18.","DOI":"10.1186\/s12890-018-0733-2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/rheumatology\/ker280","article-title":"Value of ANCA measurements during remission to predict a relapse of anca-associated vasculitis--a meta-analysis","volume":"51","author":"Tomasson","year":"2011","journal-title":"Rheumatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1002\/art.41773","article-title":"2021 American College of Rheumatology\/Vasculitis Foundation guideline for the management of Antineutrophil cytoplasmic antibody\u2013associated vasculitis","volume":"73","author":"Chung","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1136\/ard-2022-223764","article-title":"Eular recommendations for the management of Anca-Associated Vasculitis: 2022 update","volume":"83","author":"Hellmich","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1056\/NEJMoa0802311","article-title":"Azathioprine or methotrexate maintenance for ANCA-associated vasculitis","volume":"359","author":"Pagnoux","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1056\/NEJMoa1404231","article-title":"Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis","volume":"371","author":"Guillevin","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1136\/ard.2010.137778","article-title":"Long-term patient survival in ANCA-associated vasculitis","volume":"70","author":"Flossmann","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"iii74","DOI":"10.1093\/rheumatology\/kez618","article-title":"Complications of therapy for ANCA-associated vasculitis","volume":"59","author":"Smith","year":"2020","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11926-023-01123-8","article-title":"Cardiovascular disease in anti-neutrophil cytoplasm antibody-associated vasculitis","volume":"26","author":"Sayer","year":"2023","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0140-6736(03)12269-6","article-title":"Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis","volume":"361","author":"Woywodt","year":"2003","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/art.21704","article-title":"Thromboembolic events as a complication of antineutrophil cytoplasmic antibody-associated vasculitis","volume":"55","author":"Weidner","year":"2006","journal-title":"Rheum. Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJM198806233182504","article-title":"Anti-Neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis","volume":"318","author":"Falk","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1182\/blood.V74.6.1888.1888","article-title":"Wegener\u2019s granulomatosis autoantigen is a novel neutrophil serine proteinase","volume":"74","author":"Niles","year":"1989","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1073\/pnas.87.11.4115","article-title":"Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro","volume":"87","author":"Falk","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/ki.1992.52","article-title":"Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells","volume":"41","author":"Ewert","year":"1992","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1182\/blood-2016-09-741298","article-title":"Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice","volume":"129","author":"McDonald","year":"2017","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1182\/blood-2017-05-743187","article-title":"Cancer and platelet crosstalk: Opportunities and challenges for aspirin and other antiplatelet agents","volume":"131","author":"Xu","year":"2018","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/rheumatology\/kead296","article-title":"Platelet TLR7 is essential for the formation of platelet-neutrophil complexes and low-density neutrophils in lupus nephritis","volume":"63","author":"Tay","year":"2024","journal-title":"Rheumatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.thromres.2011.12.001","article-title":"Platelet-leukocyte deregulated interactions foster sterile inflammation and tissue damage in immune-mediated vessel diseases","volume":"129","author":"Maugeri","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s13075-017-1458-y","article-title":"Platelets are activated in ANCA-associated vasculitis via thrombin-PARs pathway and can activate the alternative complement pathway","volume":"19","author":"Miao","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1093\/rheumatology\/kez044","article-title":"Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis","volume":"58","author":"Miao","year":"2019","journal-title":"Rheumatology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Matsumoto, K., Yasuoka, H., Yoshimoto, K., Suzuki, K., and Takeuchi, T. (2021). Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80685-4"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102911","DOI":"10.1016\/j.autrev.2021.102911","article-title":"Monocytes and macrophages in ANCA-associated vasculitis","volume":"20","author":"Vegting","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ivanov, I.I., Apta, B.H.R., Bonna, A.M., and Harper, M.T. (2019). Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49635-7"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imr.12453","article-title":"Clearance of apoptotic neutrophils and resolution of inflammation","volume":"273","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.freeradbiomed.2024.09.009","article-title":"Neutrophil extracellular traps promote M1 macrophage polarization in gouty inflammation via targeting hexokinase-2","volume":"224","author":"Tan","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, L., Yu, X., Liu, J., Wang, Z., Li, C., Shi, J., Sun, L., Liu, Y., Zhang, F., and Chen, H. (2021). Neutrophil Extracellular Traps Promote Aberrant Macrophages Activation in Beh\u00e7et\u2019s Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.590622"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hilhorst, M., Shirai, T., Berry, G., Goronzy, J.J., and Weyand, C.M. (2014). T cell-macrophage interactions and granuloma formation in vasculitis. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00432"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1080\/25785826.2022.2094592","article-title":"Serum B cell activating factor (BAFF) as a biomarker for induction of remission with rituximab in ANCA-associated vasculitis","volume":"45","author":"Tsuboi","year":"2022","journal-title":"Immunol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa0909905","article-title":"Rituximab versus cyclophosphamide for ANCA-associated vasculitis","volume":"363","author":"Stone","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1055\/s-0038-1673386","article-title":"Pathogenesis of ANCA-Associated Pulmonary Vasculitis","volume":"39","author":"Alba","year":"2018","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/ckj\/sfz029","article-title":"T-lymphocyte in ANCA-associated vasculitis: What do we know? A pathophysiological and therapeutic approach","volume":"12","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kimoto, Y., and Horiuchi, T. (2022). The Complement System and ANCA Associated Vasculitis in the Era of Anti-Complement Drugs. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.926044"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pryzdial, E.L.G., Leatherdale, A., and Conway, E.M. (2022). Coagulation and complement: Key innate defense participants in a seamless web. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.918775"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118559","DOI":"10.1016\/j.atherosclerosis.2024.118559","article-title":"Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets","volume":"397","author":"Vegting","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sun, X.J., Chen, M., and Zhao, M.H. (2019). Thrombin Contributes to Anti-myeloperoxidase Antibody Positive IgG-Mediated Glomerular Endothelial Cells Activation Through SphK1-S1P-S1PR3 Signaling. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00237"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1365-2141.1985.tb02882.x","article-title":"The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man","volume":"61","author":"Saverymuttu","year":"1985","journal-title":"Br. J. Haematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1182\/blood-2010-01-259028","article-title":"In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days","volume":"116","author":"Pillay","year":"2010","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1172\/JCI108517","article-title":"Neutrophil kinetics in man","volume":"58","author":"Dancey","year":"1976","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1182\/blood-2003-02-0593","article-title":"Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway","volume":"102","author":"Richards","year":"2003","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1189\/jlb.0210112","article-title":"The bone marrow: A site of neutrophil clearance","volume":"88","author":"Rankin","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.it.2010.05.006","article-title":"Neutrophil kinetics in health and disease","volume":"31","author":"Summers","year":"2010","journal-title":"Trends Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"577671","DOI":"10.1016\/j.jneuroim.2021.577671","article-title":"Initial serum GM-CSF levels are associated with the severity of cerebral small vessel disease in microscopic polyangiitis patients","volume":"359","author":"Ota","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.immuni.2005.01.011","article-title":"Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17","volume":"22","author":"Stark","year":"2005","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1385\/IR:34:3:229","article-title":"IL-17A-producing neutrophil-regulatory Tn lymphocytes","volume":"34","author":"Ley","year":"2006","journal-title":"Immunol. Res."},{"key":"ref_52","first-page":"545","article-title":"Significant association between clinical characteristics and immuno-phenotypes in patients with ANCA-associated vasculitis","volume":"59","author":"Matsumoto","year":"2020","journal-title":"Rheumatology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1093\/ndt\/gfp783","article-title":"Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis","volume":"25","author":"Nogueira","year":"2010","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s10238-020-00629-0","article-title":"The association of neutrophil-to-lymphocyte ratio with all-cause mortality in Chinese patients with MPO-ANCA associated vasculitis","volume":"20","author":"Huang","year":"2020","journal-title":"Clin. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ahn, S.S., Jung, S.M., Song, J.J., Park, Y.B., and Lee, S.W. (2018). Neutrophil to lymphocyte ratio at diagnosis can estimate vasculitis activity and poor prognosis in patients with ANCA-associated vasculitis: A retrospective study. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-0992-4"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3349\/ymj.2018.59.3.397","article-title":"Delta Neutrophil Index Is Associated with Vasculitis Activity and Risk of Relapse in ANCA-Associated Vasculitis","volume":"59","author":"Yoo","year":"2018","journal-title":"Yonsei Med. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2174\/1381612053381710","article-title":"Integrins in pulmonary inflammatory diseases","volume":"11","author":"Bukiej","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: The leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1681\/ASN.2012020119","article-title":"Endothelium-neutrophil interactions in ANCA-associated diseases","volume":"23","author":"Halbwachs","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4049\/immunohorizons.2200012","article-title":"Cellular Adhesion Is a Controlling Factor in Neutrophil Extracellular Trap Formation Induced by Anti-Neutrophil Cytoplasmic Antibodies","volume":"6","author":"Lelliott","year":"2022","journal-title":"Immunohorizons"},{"key":"ref_61","first-page":"620","article-title":"ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells in vivo","volume":"127","author":"Halai","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1182\/blood-2017-03-768507","article-title":"CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation","volume":"130","author":"Bai","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1136\/annrheumdis-2016-210706","article-title":"Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis","volume":"76","author":"Nishide","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1681\/ASN.2014050477","article-title":"Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis","volume":"26","author":"Bertram","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1042\/BST20200821","article-title":"The emerging roles of semaphorin4D\/CD100 in immunological diseases","volume":"48","author":"Wang","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Li, H., Zhou, X., Huang, Y., Liao, B., Cheng, L., and Ren, B. (2021). Reactive Oxygen Species in Pathogen Clearance: The Killing Mechanisms, the Adaption Response, and the Side Effects. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.622534"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1182\/blood.V96.8.2664","article-title":"Antimicrobial proteins and peptides of blood: Templates for novel antimicrobial agents","volume":"96","author":"Levy","year":"2000","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: Specific regulators of inflammation","volume":"6","author":"Pham","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.micinf.2003.09.008","article-title":"Neutrophil granules and secretory vesicles in inflammation","volume":"5","author":"Faurschou","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41392-024-02049-y","article-title":"Neutrophil diversity and function in health and disease","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/imr.12440","article-title":"Granulopoiesis and granules of human neutrophils","volume":"273","author":"Cowland","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1189\/jlb.0810457","article-title":"Phagosome dynamics during phagocytosis by neutrophils","volume":"90","author":"Nordenfelt","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrrheum.2014.103","article-title":"Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease","volume":"10","author":"Jennette","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1681\/ASN.2011030298","article-title":"Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles","volume":"23","author":"Hong","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25377","DOI":"10.18632\/oncotarget.8298","article-title":"Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations","volume":"7","author":"Sharma","year":"2016","journal-title":"Oncotarget"},{"key":"ref_76","first-page":"295","article-title":"Lipid peroxidation and tissue damage","volume":"13","author":"Mylonas","year":"1999","journal-title":"Vivo"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0891-5849(02)00856-0","article-title":"Role of oxidative stress and protein oxidation in the aging process","volume":"33","author":"Sohal","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"22536","DOI":"10.1074\/jbc.M114.553727","article-title":"Real-time measurements of amino acid and protein hydroperoxides using coumarin boronic acid","volume":"289","author":"Michalski","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41420-021-00491-3","article-title":"ROS induces NETosis by oxidizing DNA and initiating DNA repair","volume":"7","author":"Azzouz","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"F1769","DOI":"10.1152\/ajprenal.00111.2018","article-title":"Impact of MPO-ANCA-mediated oxidative imbalance on renal vasculitis","volume":"315","author":"Hilhorst","year":"2018","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"111928","DOI":"10.1016\/j.intimp.2024.111928","article-title":"Protective effect of astaxanthin on ANCA-associated vasculitis","volume":"132","author":"Sun","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/ndt\/gfy300","article-title":"Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis","volume":"35","author":"Moran","year":"2020","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1124\/pr.112.005983","article-title":"Classification, functions, and clinical relevance of extracellular vesicles","volume":"64","author":"Harrison","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1074\/mcp.M113.028589","article-title":"Heterogeneity in neutrophil microparticles reveals distinct proteome and functional properties","volume":"12","author":"Dalli","year":"2013","journal-title":"Mol. Cell Proteom."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Soung, Y.H., Ford, S., Zhang, V., and Chung, J. (2017). Exosomes in Cancer Diagnostics. Cancers, 9.","DOI":"10.3390\/cancers9010008"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Sun, J., Sun, Z., Gareev, I., Yan, T., Chen, X., Ahmad, A., Zhang, D., Zhao, B., Beylerli, O., and Yang, G. (2021). Exosomal miR-2276-5p in Plasma Is a Potential Diagnostic and Prognostic Biomarker in Glioma. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.671202"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s13365-018-0695-4","article-title":"Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer\u2019s disease","volume":"25","author":"Pulliam","year":"2019","journal-title":"J. Neurovirol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Zheng, C., Xie, L., Qin, H., Liu, X., Chen, X., Lv, F., Wang, L., Zhu, X., and Xu, J. (2022). The Role of Extracellular Vesicles in Systemic Lupus Erythematosus. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.835566"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ricco, C., Eldaboush, A., Liu, M.L., and Werth, V.P. (2024). Extracellular Vesicles in the Pathogenesis, Clinical Characterization, and Management of Dermatomyositis: A Narrative Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25041967"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1080\/09537104.2016.1254174","article-title":"Platelet extracellular vesicles as biomarkers for arterial thrombosis","volume":"28","author":"Gasecka","year":"2017","journal-title":"Platelets"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/03009742.2022.2045790","article-title":"Pentraxin-3\u2014A potential biomarker in ANCA-associated vasculitis","volume":"52","author":"Jonasdottir","year":"2023","journal-title":"Scand. J. Rheumatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s00109-020-01955-2","article-title":"Microparticles expressing myeloperoxidase as potential biomarkers in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)","volume":"98","author":"Manojlovic","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"714","DOI":"10.3899\/jrheum.181347","article-title":"Microparticles Expressing Myeloperoxidase and Complement C3a and C5a as Markers of Renal Involvement in Antineutrophil Cytoplasmic Antibody-associated Vasculitis","volume":"47","author":"Antovic","year":"2020","journal-title":"J. Rheumatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1194\/jlr.M092072","article-title":"LTB4 and 5-oxo-ETE from extracellular vesicles stimulate neutrophils in granulomatosis with polyangiitis","volume":"61","author":"Surmiak","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/cei.13581","article-title":"Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis","volume":"204","author":"Surmiak","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/cei\/uxac022","article-title":"Profile of circulating extracellular vesicles microRNA correlates with the disease activity in granulomatosis with polyangiitis","volume":"208","author":"Surmiak","year":"2022","journal-title":"Clin. Exp. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102826","DOI":"10.1016\/j.jaut.2022.102826","article-title":"Neutrophil-derived extracellular vesicles induce endothelial inflammation and damage through the transfer of miRNAs","volume":"129","author":"Gavard","year":"2022","journal-title":"J. Autoimmun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.cell.2013.04.040","article-title":"Rhythmic modulation of the hematopoietic niche through neutrophil clearance","volume":"153","author":"Pitaval","year":"2013","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature15367","article-title":"Neutrophil ageing is regulated by the microbiome","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Aroca-Crevill\u00e9n, A., Adrover, J.M., and Hidalgo, A. (2020). Circadian Features of Neutrophil Biology. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00576"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1084\/jem.20130056","article-title":"Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow","volume":"210","author":"Devi","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1136\/ard.52.5.354","article-title":"Receptor expression in synovial fluid neutrophils from patients with rheumatoid arthritis","volume":"52","author":"Watson","year":"1993","journal-title":"Ann. Rheum. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1365-2249.2008.03791.x","article-title":"Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease","volume":"155","author":"Fortunati","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ajpath.2023.10.009","article-title":"Phenotypic and Functional Diversity of Neutrophils in Gut Inflammation and Cancer","volume":"194","author":"Sumagin","year":"2024","journal-title":"Am. J. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Dahlstrand Rudin, A., Torell, A., Popovic, J., Stockfelt, M., Jacobsson, B., Rudin, A., Christenson, K., Lundell, A.C., and Bylund, J. (2025). Pregnancy is associated with a simultaneous but independent increase in circulating CD177pos and immature low-density granulocytes. J. Leukoc. Biol., 117.","DOI":"10.1093\/jleuko\/qiae255"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1365-2141.2004.05027.x","article-title":"Neutrophil CD177 (NB1 gp, HNA-2a) expression is increased in severe bacterial infections and polycythaemia vera","volume":"126","author":"Wolff","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1365-2249.2010.04154.x","article-title":"Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression","volume":"161","author":"Abdgawad","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1681\/ASN.V1061224","article-title":"A large subset of neutrophils expressing membrane proteinase 3 is a risk factor for vasculitis and rheumatoid arthritis","volume":"10","author":"Lesavre","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6648265","DOI":"10.1155\/2024\/6648265","article-title":"Disease Activity and Tendency to Relapse in ANCA-Associated Vasculitis Are Reflected in Neutrophil and Intermediate Monocyte Frequencies","volume":"2024","author":"Smargianaki","year":"2024","journal-title":"J. Immunol. Res."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Marino, S.F., Jerke, U., Rolle, S., Daumke, O., and Kettritz, R. (2022). Competitively disrupting the neutrophil-specific receptor-autoantigen CD177, proteinase 3 membrane complex reduces anti-PR3 antibody-induced neutrophil activation. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101598"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1074\/jbc.M110.171256","article-title":"Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation","volume":"286","author":"Jerke","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13075-021-02510-1","article-title":"Identification of neutrophil \u03b22-integrin LFA-1 as a potential mechanistic biomarker in ANCA-associated vasculitis via microarray and validation analyses","volume":"23","author":"Matsumoto","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1681\/ASN.V7140","article-title":"Circulating leukocyte integrin expression in Wegener\u2019s granulomatosis","volume":"7","author":"Haller","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"c222","DOI":"10.1159\/000235242","article-title":"Expression of tumor necrosis factor receptors on granulocytes in patients with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis","volume":"113","author":"Hasegawa","year":"2009","journal-title":"Nephron. Clin. Pract."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/art.1780291105","article-title":"Low density neutrophils in patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever","volume":"29","author":"Hacbarth","year":"1986","journal-title":"Rheum. Arthritis Rheum."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e202302332","DOI":"10.26508\/lsa.202302332","article-title":"Immunosuppressive low-density neutrophils in the blood of cancer patients display a mature phenotype","volume":"7","author":"Vanhaver","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Sun, R., Huang, J., Yang, Y., Liu, L., Shao, Y., Li, L., and Sun, B. (2022). Dysfunction of low-density neutrophils in peripheral circulation in patients with sepsis. Sci. Rep., 12.","DOI":"10.1038\/s41598-021-04682-x"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1189\/jlb.5A0116-022R","article-title":"Low-density granulocytes: Functionally distinct, immature neutrophils in rheumatoid arthritis with altered properties and defective TNF signalling","volume":"101","author":"Wright","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1016\/j.jid.2022.04.011","article-title":"A Distinct Immature Low-Density Neutrophil Population Characterizes Acute Generalized Pustular Psoriasis","volume":"142","author":"Yu","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/rheumatology\/keaa324","article-title":"Elevated circulating pro-inflammatory low-density granulocytes in adult-onset Still\u2019s disease","volume":"60","author":"Liu","year":"2021","journal-title":"Rheumatology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.4049\/jimmunol.0902199","article-title":"A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs","volume":"184","author":"Denny","year":"2010","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4049\/jimmunol.1100450","article-title":"Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus","volume":"187","author":"Villanueva","year":"2011","journal-title":"J. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1097\/RHU.0000000000001772","article-title":"Low-Density Granulocytes and Neutrophil Extracellular Traps as Biomarkers of Disease Activity in Adult Inflammatory Myopathies","volume":"28","year":"2022","journal-title":"J. Clin. Rheumatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"331ra40","DOI":"10.1126\/scitranslmed.aae0482","article-title":"Arginase-1-dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus","volume":"8","author":"Wu","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Ui Mhaonaigh, A., Coughlan, A.M., Dwivedi, A., Hartnett, J., Cabral, J., Moran, B., Brennan, K., Doyle, S.L., Hughes, K., and Lucey, R. (2019). Low Density Granulocytes in ANCA Vasculitis Are Heterogenous and Hypo-Responsive to Anti-Myeloperoxidase Antibodies. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02603"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"R140","DOI":"10.1186\/ar3873","article-title":"C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis","volume":"14","author":"Yuan","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1002\/art.39153","article-title":"Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated with Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis","volume":"67","author":"Grayson","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Blanco-Camarillo, C., Alem\u00e1n, O.R., and Rosales, C. (2021). Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.672520"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.it.2019.04.012","article-title":"Neutrophil Diversity in Health and Disease","volume":"40","author":"Fridlender","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Hardisty, G.R., Llanwarne, F., Minns, D., Gillan, J.L., Davidson, D.J., Gwyer Findlay, E., and Gray, R.D. (2021). High Purity Isolation of Low Density Neutrophils Casts Doubt on Their Exceptionality in Health and Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.625922"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Figueroa, E., \u00c1lvarez-Carrasco, P., Ortega, E., and Maldonado-Bernal, C. (2021). Neutrophils: Many Ways to Die. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.631821"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Abdgawad, M., Pettersson, \u00c5., Gunnarsson, L., Bengtsson, A.A., Geborek, P., Nilsson, L., Segelmark, M., and Hellmark, T. (2012). Decreased neutrophil apoptosis in quiescent ANCA-associated systemic vasculitis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032439"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/03009742.2019.1634219","article-title":"Delayed neutrophil apoptosis in granulomatosis with polyangiitis: Dysregulation of neutrophil gene signature and circulating apoptosis-related proteins","volume":"49","author":"Surmiak","year":"2020","journal-title":"Scand. J. Rheumatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_136","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_137","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1007\/s10753-020-01294-x","article-title":"The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms","volume":"43","author":"Cahilog","year":"2020","journal-title":"Inflammation"},{"key":"ref_138","first-page":"S98","article-title":"Neutrophil-related and serum biomarkers in granulomatosis with polyangiitis support extracellular traps mechanism of the disease","volume":"34","author":"Surmiak","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.kint.2018.01.013","article-title":"Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA","volume":"94","author":"Kraaij","year":"2018","journal-title":"Kidney Int."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm.1959","article-title":"Netting neutrophils in autoimmune small-vessel vasculitis","volume":"15","author":"Kessenbrock","year":"2009","journal-title":"Nat. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.kint.2023.03.029","article-title":"Assessment of longitudinal serum neutrophil extracellular trap-inducing activity in anti-neutrophil cytoplasmic antibody-associated vasculitis and glomerulonephritis in a prospective cohort using a novel bio-impedance technique","volume":"104","author":"Aendekerk","year":"2023","journal-title":"Kidney Int."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/cei.12628","article-title":"Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis","volume":"181","author":"Surmiak","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Ford, S.L., O\u2019Sullivan, K.M., Kitching, A.R., Holdsworth, S.R., Gan, P.Y., and Summers, S.A. (2023). Toll-like Receptor 9 Induced Dendritic Cell Activation Promotes Anti-Myeloperoxidase Autoimmunity and Glomerulonephritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021339"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/cdd.2009.96","article-title":"Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps","volume":"16","author":"Yousefi","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Gajendran, C., Fukui, S., Sadhu, N.M., Zainuddin, M., Rajagopal, S., Gosu, R., Gutch, S., Fukui, S., Sheehy, C.E., and Chu, L. (2023). Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30246-2"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Pan, T., Tuoerxun, T., Chen, X., Yang, C.J., Jiang, C.Y., Zhu, Y.F., Li, Z.S., Jiang, X.Y., Zhang, H.T., and Zhang, H. (2023). The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass. Front. Immunol., 14, Erratum in Front. Immunol. 2023, 14, 1165081.","DOI":"10.3389\/fimmu.2023.1082830"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1721727X241237437","DOI":"10.1177\/1721727X241237437","article-title":"Therapeutic potential of elafin in airway inflammatory disease","volume":"22","author":"He","year":"2024","journal-title":"Eur. J. Inflamm."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1681\/ASN.2021081112","article-title":"Targeting Cathepsin C in PR3-ANCA Vasculitis","volume":"33","author":"Jerke","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/art.42321","article-title":"Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis","volume":"75","author":"Prendecki","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.kint.2019.12.014","article-title":"Spleen tyrosine kinase inhibition is an effective treatment for established vasculitis in a pre-clinical model","volume":"97","author":"McAdoo","year":"2020","journal-title":"Kidney Int."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1681\/ASN.2008050497","article-title":"C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis","volume":"20","author":"Schreiber","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1016\/j.ekir.2024.07.007","article-title":"Avacopan in Anti-Neutrophil Cytoplasmic Autoantibodies-Associated Vasculitis in a Real-World Setting","volume":"9","author":"Zimmermann","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/CIRCRESAHA.124.323579","article-title":"What It Takes to Be a Platelet: Evolving Concepts in Platelet Production","volume":"135","author":"Carminita","year":"2024","journal-title":"Circ. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1111\/jth.14544","article-title":"New insights into cytoskeletal remodeling during platelet production","volume":"17","author":"Ghalloussi","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3109\/03009742.2015.1006247","article-title":"Platelet counts as a biomarker in ANCA-associated vasculitis","volume":"44","author":"Willeke","year":"2015","journal-title":"Scand. J. Rheumatol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1182\/blood-2015-05-644583","article-title":"CCL5 derived from platelets increases megakaryocyte proplatelet formation","volume":"127","author":"Machlus","year":"2016","journal-title":"Blood"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"88","DOI":"10.55563\/clinexprheumatol\/m46d0v","article-title":"Pan-immune-inflammation value at diagnosis independently predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis","volume":"39","author":"Lee","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s42358-019-0110-8","article-title":"Platelet\/lymphocyte ratio and mean platelet volume in patients with granulomatosis with polyangiitis","volume":"60","author":"Kucuk","year":"2019","journal-title":"Adv. Rheumatol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00296-018-4125-y","article-title":"Platelet to lymphocyte ratio is associated with the current activity of ANCA-associated vasculitis at diagnosis: A retrospective monocentric study","volume":"38","author":"Park","year":"2018","journal-title":"Rheumatol. Int."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s10238-024-01333-z","article-title":"Low platelet count at diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis is correlated with the severity of disease and renal prognosis","volume":"24","author":"Jin","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1093\/ndt\/gfac320","article-title":"Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis","volume":"38","author":"Moi","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1007\/s00018-010-0306-x","article-title":"Platelet-derived chemokines: Pathophysiology and therapeutic aspects","volume":"67","author":"Flad","year":"2010","journal-title":"Cell Mol. Life Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.pbj.2017.05.005","article-title":"Role of platelets in immune system and inflammation","volume":"2","author":"Sonmez","year":"2017","journal-title":"Porto Biomed. J."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1111\/jth.13147","article-title":"Platelet secretory behaviour: As diverse as the granules \u2026 or not?","volume":"13","author":"Heijnen","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"102261","DOI":"10.1016\/j.rpth.2023.102261","article-title":"Platelets from patients with chronic inflammation have a phenotype of chronic IL-1\u03b2 release","volume":"8","author":"Berger","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1182\/blood.V96.13.4046","article-title":"Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets","volume":"96","author":"Clemetson","year":"2000","journal-title":"Blood"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.exphem.2006.06.015","article-title":"Platelet FcgammaRIIA binds and internalizes IgG-containing complexes","volume":"34","author":"Worth","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nm1565","article-title":"Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"Clark","year":"2007","journal-title":"Nat. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"254","DOI":"10.4049\/jimmunol.138.1.254","article-title":"Cellular distribution of complement receptor type 4 (CR4): Expression on human platelets","volume":"138","author":"Vik","year":"1987","journal-title":"J. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0171-2985(98)80030-2","article-title":"Platelet receptors for the complement component C1q: Implications for hemostasis and thrombosis","volume":"199","author":"Peerschke","year":"1998","journal-title":"Immunobiology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1084\/jem.20041497","article-title":"Platelet activation leads to activation and propagation of the complement system","volume":"201","author":"Zhang","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_172","first-page":"160","article-title":"Complement in vasculitis associated with anti-neutrophil cytoplasm antibodies with renal involvement: Pathogenic, prognostic and therapeutic implications","volume":"161","year":"2023","journal-title":"Med. Clin."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1161\/ATVBAHA.120.314647","article-title":"Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease","volume":"41","author":"Aslan","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s12967-023-04059-w","article-title":"Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype","volume":"21","author":"Cornwell","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1182\/blood-2018-99-117833","article-title":"Phenotype of platelets are altered and activated in circulation of patients with systemic sclerosis","volume":"132","author":"Yasuoka","year":"2018","journal-title":"Blood"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3109\/09537104.2016.1171302","article-title":"Platelet phenotype changes associated with breast cancer and its treatment","volume":"27","author":"Holmes","year":"2016","journal-title":"Platelets"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nm.2184","article-title":"Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases","volume":"16","author":"Massberg","year":"2010","journal-title":"Nat. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","article-title":"Neutrophil extracellular traps promote deep vein thrombosis in mice","volume":"10","author":"Brill","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1002\/art.39239","article-title":"Promotion of hypercoagulability in antineutrophil cytoplasmic antibody-associated vasculitis by C5a-induced tissue factor-expressing microparticles and neutrophil extracellular traps","volume":"67","author":"Huang","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_180","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_181","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3899\/jrheum.100735","article-title":"Relationship between markers of platelet activation and inflammation with disease activity in Wegener\u2019s granulomatosis","volume":"38","author":"Tomasson","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Liu, X., Gorzelanny, C., and Schneider, S.W. (2019). Platelets in Skin Autoimmune Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01453"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cca.2008.09.018","article-title":"Soluble P-selectin as a marker of in vivo platelet activation","volume":"399","author":"Ferroni","year":"2009","journal-title":"Clin. Chim. Acta"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1161\/ATVBAHA.110.211615","article-title":"P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease","volume":"30","author":"Wallace","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-selectin promotes neutrophil extracellular trap formation in mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"L342","DOI":"10.1152\/ajplung.00151.2012","article-title":"HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4","volume":"304","author":"Tadie","year":"2013","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2119\/molmed.2010.00132","article-title":"High-mobility group box-1 protein (HMGB1) is increased in antineutrophilic cytoplasmatic antibody (ANCA)-associated vasculitis with renal manifestations","volume":"17","author":"Bruchfeld","year":"2011","journal-title":"Mol. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1600-0609.2012.01817.x","article-title":"Comparative evaluation of the role of the adhesion molecule CD177 in neutrophil interactions with platelets and endothelium","volume":"89","author":"Pliyev","year":"2012","journal-title":"Eur. J. Haematol."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Al-Soudi, A., Vegting, Y., Klarenbeek, P.L., and Hilhorst, M.L. (2022). Do Relapses Follow ANCA Rises? A Systematic Review and Meta-Analysis on the Value of Serial ANCA Level Evaluation. Front. Med., 9.","DOI":"10.3389\/fmed.2022.844112"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.nefroe.2021.07.005","article-title":"The neutrophil-to-lymphocyte ratio as a marker of vasculitis activity, severe infection and mortality in anca-associated vasculitis: A retrospective study","volume":"41","author":"Fonseca","year":"2021","journal-title":"Nefrol. (Engl. Ed.)"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/15\/1905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:18:30Z","timestamp":1760033910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/15\/1905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":190,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["diagnostics15151905"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15151905","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]}}}