{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:59:18Z","timestamp":1785452358439,"version":"3.56.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013514","name":"Columbus Medical Association Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Antineutrophil cytoplasmic antibody (ANCA)\u2013associated vasculitis often leads to severe kidney damage. To better understand ANCA\u2010associated glomerulonephritis (AAGN) and identify potential new therapeutic targets, we performed comprehensive transcriptomic and compartmental proteomic analysis of kidney biopsies from 23 patients in the transcriptomic cohort, 10 in the proteomic cohort, and 5 healthy controls for each comparison.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk RNA sequencing was performed on formalin\u2010fixed paraffin\u2010embedded kidney biopsies. Differentially expressed genes and pathways were identified using DESeq2, Ingenuity Pathway Analysis, and gene set enrichment analysis (GSEA). Correlations between gene expression and histologic features were assessed. Proteomic analysis was conducted via mass spectrometry of laser\u2010microdissected glomerular and tubulointerstitial compartments to identify differentially abundant proteins and enriched pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In AAGN, 347 genes were up\u2010regulated and 134 down\u2010regulated compared to controls, including\n                      <jats:italic>IL17D, CXCR2, IL7R,<\/jats:italic>\n                      and\n                      <jats:italic>CD163<\/jats:italic>\n                      . Notably, several tripartite motif (TRIM) family genes were up\u2010regulated. GSEA revealed broad immune cell enrichment and activation of proinflammatory interleukin (IL)\u201012, IL\u201017, and IL\u201018 signaling. Additionally, specific pathways correlated with histologic features (r \u2265 0.6), including enrichment of the complement cascade in histologically normal glomeruli, suggesting complement activation precedes visible structural damage. Conversely, STAT3\/TRIM25 signaling correlated with glomerulosclerosis, IL\u201023 with necrotizing glomeruli, and FAT10 (UBD) signaling with interstitial fibrosis and tubular atrophy. Proteomics identified 63 differentially abundant proteins in the tubulointerstitium and 271 in glomeruli, with key network activators overlapping across data sets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study uncovered a complex intrarenal immune landscape in AAGN, featuring diverse immune cell involvement and pathways associated with progressive damage. Our findings highlight potential therapeutic targets for further investigation, including IL\u201017, IL\u20108, and IL\u201023.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr290114-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.90114","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:16:02Z","timestamp":1784801762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Combined Transcriptomics and Proteomics Approach to Identify Immune Signatures in\n                    <scp>ANCA<\/scp>\n                    \u2010Associated Glomerulonephritis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9033-6168","authenticated-orcid":false,"given":"Ivana","family":"Stojkic","sequence":"first","affiliation":[{"name":"Division of Pediatric Rheumatology Nationwide Children's Hospital  Columbus Ohio"},{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Arazi","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research  Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Song","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearlly","family":"Yan","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Puchulu\u2010Campanella","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubao","family":"Wang","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Smoyer","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital  Columbus Ohio"},{"name":"Division of Pediatric Nephrology Nationwide Children's Hospital  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-0216","authenticated-orcid":false,"given":"Lynn A.","family":"Fussner","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Satoskar","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Abigail Wexner Research Institute at Nationwide Children's Hospital  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-525X","authenticated-orcid":false,"given":"Samir V.","family":"Parikh","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy P.","family":"Ardoin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology Nationwide Children's Hospital  Columbus Ohio"},{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Koboldt","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology Nationwide Children's Hospital  Columbus Ohio"},{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-0210","authenticated-orcid":false,"given":"Brad H.","family":"Rovin","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center  Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Almaani","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-6-488"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909905"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(24)00025-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(24)00035-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw046"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199711203372106"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(03)00025-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.008"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165402"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000910"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52525-w"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000116"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0398-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0232-6"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0378-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1013660"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214539"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71833"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010050477"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102914"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015319"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13170"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1261151"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2054431"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2018.1450631"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b05028"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2025.344227"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2023386"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1031445"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159751"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2020.1748597"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197319"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00098"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090585"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.09.038"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03251-5"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513943113"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2025.07.034"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032975"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.673912"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-022-00908-y"}],"container-title":["ACR Open Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.90114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acr2.90114","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.90114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:25:33Z","timestamp":1785450333000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr2.90114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/acr2.90114"],"URL":"https:\/\/doi.org\/10.1002\/acr2.90114","archive":["Portico"],"relation":{},"ISSN":["2578-5745","2578-5745"],"issn-type":[{"value":"2578-5745","type":"print"},{"value":"2578-5745","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e90114"}}