{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:35Z","timestamp":1792787315218,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"unspecified","delay-in-days":84,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Greek Rheumatology Society and the Greek Association of Professional Rheumatologists"},{"name":"Special Account for Research Grants, National and Kapodistrian University of Athens, Athens, Greece","award":["12085"],"award-info":[{"award-number":["12085"]}],"id":[{"id":"https:\/\/ror.org\/04gnjpq42","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Special Account for Research Grants, National and Kapodistrian University of Athens, Athens, Greece","award":["12086"],"award-info":[{"award-number":["12086"]}],"id":[{"id":"https:\/\/ror.org\/04gnjpq42","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The pathogenesis of relapses in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) remains ill defined. We aimed to identify whether there are any differences in the molecular profile between patients with relapsing versus new-onset disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole blood RNA sequencing in 21 patients with MPA or GPA and 12 age-matched\/sex-matched healthy controls was performed; 11 patients had active disease, either newly diagnosed (treatment-na\u00efve, n=6) or relapsed (off-therapy, n=5) and 10 were in remission, either on (n=4) or off (n=6) maintenance therapy. Differential gene expression and functional enrichment analysis were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Relapsing patients with MPA\/GPA exhibited a distinct molecular profile compared with healthy controls, newly diagnosed patients or those in remission. Specifically, patients with a major relapse displayed a unique pattern of 41 neutrophil degranulation-associated genes, encoding neutrophil granular proteins, proteins mediating neutrophil adhesion and chemotaxis and proteins involved in myelopoiesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this well-defined MPA\/GPA cohort, we report for the first time a distinct relapse-associated transcriptional signature consistent with enhanced neutrophil activity. Therapies targeting neutrophil activation could represent a novel approach for preventing or treating relapses in MPA\/GPA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2026-007063","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:41Z","timestamp":1790179841000},"page":"e007063","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct molecular signature in relapsed patients with ANCA-associated vasculitis"],"prefix":"10.1136","volume":"12","author":[{"given":"Chrysoula G","family":"Gialouri","sequence":"first","affiliation":[{"name":"Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Valakos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savvina","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-6918","authenticated-orcid":false,"given":"Christos","family":"Koutsianas","sequence":"additional","affiliation":[{"name":"Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Chalkia","sequence":"additional","affiliation":[{"name":"Nephrology Department, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Petras","sequence":"additional","affiliation":[{"name":"Nephrology Department, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios T","family":"Boumpas","sequence":"additional","affiliation":[{"name":"Joint Rheumatology Program, 4th Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Attikon General Hospital, Athens, Greece"},{"name":"Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-6505","authenticated-orcid":false,"given":"Aggelos","family":"Banos","sequence":"additional","affiliation":[{"name":"Joint Rheumatology Program, 4th Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Attikon General Hospital, Athens, Greece"},{"name":"Laboratory of Autoimmunity and Inflammation, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-3863","authenticated-orcid":false,"given":"Dimitrios","family":"Vassilopoulos","sequence":"additional","affiliation":[{"name":"Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens \u201cHippokration\u201d, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092309101076000_12.3.e007063.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00819-y"},{"key":"2026092309101076000_12.3.e007063.2","doi-asserted-by":"crossref","first-page":"106933","DOI":"10.1016\/j.imlet.2024.106933","article-title":"The role of neutrophils in ANCA-associated vasculitis","volume":"270","author":"Prendecki","year":"2024","journal-title":"Immunol Lett"},{"key":"2026092309101076000_12.3.e007063.3","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/ndt\/gfad237","article-title":"ANCA-associated vasculitis-treatment standard","volume":"39","author":"Chalkia","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2026092309101076000_12.3.e007063.4","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/rheumatology\/keae409","article-title":"Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study","volume":"64","author":"Gialouri","year":"2025","journal-title":"Rheumatology (Oxford)"},{"key":"2026092309101076000_12.3.e007063.5","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224816"},{"key":"2026092309101076000_12.3.e007063.6","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1072598","article-title":"The genomic landscape of ANCA-associated vasculitis: distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus","volume":"14","author":"Banos","year":"2023","journal-title":"Front Immunol"},{"key":"2026092309101076000_12.3.e007063.7","doi-asserted-by":"crossref","first-page":"102617","DOI":"10.1016\/j.jaut.2021.102617","article-title":"Identifying the most influential gene expression profile in distinguishing ANCA-associated vasculitis from healthy controls","volume":"119","author":"Yanaoka","year":"2021","journal-title":"J Autoimmun"},{"key":"2026092309101076000_12.3.e007063.8","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":"2026092309101076000_12.3.e007063.9","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-41328-0","article-title":"Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis","volume":"14","author":"Nishide","year":"2023","journal-title":"Nat Commun"},{"key":"2026092309101076000_12.3.e007063.10","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-58550-7","article-title":"Neutrophil single-cell analysis identifies a type II interferon-related subset for predicting relapse of autoimmune small vessel vasculitis","volume":"16","author":"Nishide","year":"2025","journal-title":"Nat Commun"},{"key":"2026092309101076000_12.3.e007063.11","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221796"},{"key":"2026092309101076000_12.3.e007063.12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221795"},{"key":"2026092309101076000_12.3.e007063.13","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223764"},{"key":"2026092309101076000_12.3.e007063.14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1089\/bio.2019.0029","article-title":"Quality control of RNA extracted from PAXgene blood RNA tubes after different storage periods","volume":"17","author":"Tang","year":"2019","journal-title":"Biopreserv Biobank"},{"key":"2026092309101076000_12.3.e007063.15","unstructured":"Biosciences B . PAXgene blood RNA tube. n.d. Available: https:\/\/www.bdbiosciences.com\/en-eu\/products\/blood-collection\/blood-collection-tubes\/paxgene-blood-rna-tube.762165?tab=product_details"},{"key":"2026092309101076000_12.3.e007063.16","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"2026092309101076000_12.3.e007063.17","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"2026092309101076000_12.3.e007063.18","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026092309101076000_12.3.e007063.19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"2026092309101076000_12.3.e007063.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"2026092309101076000_12.3.e007063.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0145-y"},{"key":"2026092309101076000_12.3.e007063.22","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.ekir.2019.01.004","article-title":"Understanding long-term remission off therapy in antineutrophil cytoplasmic antibody-associated vasculitis","volume":"4","author":"Hogan","year":"2019","journal-title":"Kidney Int Rep"},{"key":"2026092309101076000_12.3.e007063.23","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.autrev.2019.06.011","article-title":"An emerging role of neutrophils and NETosis in chronic inflammation and fibrosis in systemic lupus erythematosus (SLE) and ANCA-associated vasculitides (AAV): Implications for the pathogenesis and treatment","volume":"18","author":"Frangou","year":"2019","journal-title":"Autoimmun Rev"},{"key":"2026092309101076000_12.3.e007063.24","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.635188","article-title":"Neutrophil extracellular traps: a potential therapeutic target in MPO-ANCA-associated vasculitis?","volume":"12","author":"O\u2019Sullivan","year":"2021","journal-title":"Front Immunol"},{"key":"2026092309101076000_12.3.e007063.25","doi-asserted-by":"crossref","DOI":"10.1111\/eci.14349","article-title":"The role of CEACAMs in neutrophil function","volume":"54 Suppl 2","author":"Skubitz","year":"2024","journal-title":"Eur J Clin Invest"},{"key":"2026092309101076000_12.3.e007063.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118677"},{"key":"2026092309101076000_12.3.e007063.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401847"},{"key":"2026092309101076000_12.3.e007063.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01311-1"},{"key":"2026092309101076000_12.3.e007063.29","doi-asserted-by":"crossref","first-page":"366","DOI":"10.31138\/mjr.31.3.366","article-title":"Mitophagy balance in various cell subsets in patients with ANCA-associated vasculitis and correlation with the presence of anti-neutrophil cytoplasmic antibodies","volume":"31","author":"Banos","year":"2020","journal-title":"Mediterr J Rheumatol"},{"key":"2026092309101076000_12.3.e007063.30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.kint.2025.07.034","article-title":"A stronger type I interferon signature distinguishes ANCA-associated vasculitis phenotypes and predicts kidney prognosis","volume":"109","author":"Brilland","year":"2026","journal-title":"Kidney Int"},{"key":"2026092309101076000_12.3.e007063.31","doi-asserted-by":"crossref","first-page":"103824","DOI":"10.1016\/j.autrev.2025.103824","article-title":"The emerging concept of ANCA-associated vasculitis related to inborn errors of immunity","volume":"24","author":"Triaille","year":"2025","journal-title":"Autoimmun Rev"},{"key":"2026092309101076000_12.3.e007063.32","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-07505-2","article-title":"Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression","volume":"9","author":"Rice","year":"2018","journal-title":"Nat Commun"},{"key":"2026092309101076000_12.3.e007063.33","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13142"},{"key":"2026092309101076000_12.3.e007063.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6"},{"key":"2026092309101076000_12.3.e007063.35","doi-asserted-by":"publisher","DOI":"10.31138\/mjr.33.2.176"},{"key":"2026092309101076000_12.3.e007063.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.018"},{"key":"2026092309101076000_12.3.e007063.37","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1093\/rheumatology\/kead015","article-title":"Mitochondrial DNA: a novel indicator of active inflammation in ANCA-associated vasculitides","volume":"62","author":"Giaglis","year":"2023","journal-title":"Rheumatology (Oxford)"},{"key":"2026092309101076000_12.3.e007063.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0412-0"},{"key":"2026092309101076000_12.3.e007063.39","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19124090","article-title":"How glucocorticoids affect the neutrophil life","volume":"19","author":"Ronchetti","year":"2018","journal-title":"Int J Mol Sci"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2026-007063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:44Z","timestamp":1790179844000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2026-007063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9,23]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1136\/rmdopen-2026-007063"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2026-007063","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}