{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:07:19Z","timestamp":1779354439938,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/30\/M\/NZ1\/00367"],"award-info":[{"award-number":["2018\/30\/M\/NZ1\/00367"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2019\/34\/H\/NZ1\/00674"],"award-info":[{"award-number":["2019\/34\/H\/NZ1\/00674"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["296129"],"award-info":[{"award-number":["296129"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE 022597"],"award-info":[{"award-number":["DE 022597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017\u201000359"],"award-info":[{"award-number":["2017\u201000359"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["772209"],"award-info":[{"award-number":["772209"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Enzymes like peptidylarginine deiminase 4 (PAD4) generate citrullinated epitopes that are crucial in triggering and driving the anti\u2010citrullinated protein antibody (ACPA) response in rheumatoid arthritis. Here, we assessed whether serum PAD4\u2010potentiating activity is associated with subsequent arthritis development among ACPA\u2010positive individuals during the pre\u2010clinical phase. The study included 267 ACPA\u2010positive individuals from the Karolinska Risk\u2010RA cohort, among whom 101 (37.8%) developed arthritis within the observational period (range 22\u201360\u2009months). We measured the ability of serum to potentiate PAD4 activity by quantifying the generation of citrullinated products using high\u2010performance HPLC. Study participants were then classified as PAD4\n                    <jats:sub>act<\/jats:sub>\n                    \u2010positive or \u2010negative, and PAD4 status analysed in relation to onset of arthritis, clinical characteristics (ESR, CRP and DAS28) and established risk factors (HLA\u2010DRB genotype, smoking). PAD4\n                    <jats:sub>act<\/jats:sub>\n                    \u2010positivity was identified in 35 individuals, with a significant proportion (21,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0049) developing arthritis. Kaplan\u2013Meier analysis demonstrated that individuals with PAD4\n                    <jats:sub>act<\/jats:sub>\n                    \u2010positivity had increased rate of progressing to arthritis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0022). Additionally, PAD4\n                    <jats:sub>act<\/jats:sub>\n                    \u2010positive individuals were more likely to possess at least one copy of the HLA\u2010DRB shared epitope allele (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.045). Notably, PAD4\n                    <jats:sub>act<\/jats:sub>\n                    \u2010positivity did not associate with pre\u2010clinical CRP, ESR, DAS28, or smoking status. These findings suggest that serum PAD4\u2010potentiating activity may help stratify arthritis risk and time to onset among ACPA\u2010positive at\u2010risk individuals.\n                  <\/jats:p>","DOI":"10.1111\/sji.70119","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T03:33:48Z","timestamp":1779161628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Biomarker for Rheumatoid Arthritis: Serum Peptidylarginine Deiminase 4\u2010Potentiating Activity in an Anti\u2010Citrullinated Protein Antibody\u2010Positive At\u2010Risk Population"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-7603","authenticated-orcid":false,"given":"Marta","family":"Kaminska","sequence":"first","affiliation":[{"name":"Broegelmann Research Laboratory, Department of Clinical Science, Faculty of Medicine University of Bergen  Bergen Norway"},{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay","family":"Joshua","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Bielecka","sequence":"additional","affiliation":[{"name":"Ma\u0142opolska Centre of Biotechnology Jagiellonian University  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Kantyka","sequence":"additional","affiliation":[{"name":"Ma\u0142opolska Centre of Biotechnology Jagiellonian University  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Chrobak","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Division of Rheumatology Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7669-3777","authenticated-orcid":false,"given":"Aase","family":"Hensvold","sequence":"additional","affiliation":[{"name":"Center for Rheumatology Academic Specialist Center, Stockholm Health Services  Region Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Krak\u00f3w Poland"},{"name":"Department of Oral Immunity &amp; Infectious Diseases University of Louisville School of Dentistry  Louisville Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-9391","authenticated-orcid":false,"given":"Piotr","family":"Mydel","sequence":"additional","affiliation":[{"name":"Broegelmann Research Laboratory, Department of Clinical Science, Faculty of Medicine University of Bergen  Bergen Norway"},{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010023\u201003140\u20105"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12082781"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010021\u201002612\u2010w"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2751"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010223356"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665\u20109913(23)00211\u20104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41571"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102015\u2010208980"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0287707"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2017.72807"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201059542\u20109_2"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010020\u20100409\u20101"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022\u2010202X.2004.23568.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173765"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666151118120710"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/895343"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1167362"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517747575"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.804822"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq8476"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314560005"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2019.1641216"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae146"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020475"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010016\u20101177\u20109"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901108"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20230209"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2023.2247986"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047337\u2010x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)02650\u20108"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010023\u201001535\u20108"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010021\u201002528\u20105"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","unstructured":"G. P.Bereta E.Bielecka K.Marzec et\u00a0al. \u201cGlycosaminoglycans Act as Activators of Peptidylarginine Deiminase 4. bioRxiv \u201d(2024) https:\/\/doi.org\/10.1101\/2024.06.17.599283.","DOI":"10.1101\/2024.06.17.599283"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11144213"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890\u2010023\u201002594\u20102"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.12.010"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead545"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11630"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010015\u20103082\u2010z"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.075192"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131241"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2023.2235734"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358\u2010024\u201000352\u20104"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae113"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2022.2127245"}],"container-title":["Scandinavian Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/sji.70119","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/sji.70119","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/sji.70119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:10:51Z","timestamp":1779351051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/sji.70119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/sji.70119"],"URL":"https:\/\/doi.org\/10.1111\/sji.70119","archive":["Portico"],"relation":{},"ISSN":["0300-9475","1365-3083"],"issn-type":[{"value":"0300-9475","type":"print"},{"value":"1365-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70119"}}