{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:18:54Z","timestamp":1740136734521,"version":"3.37.3"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 77700","MOP 77700","MOP 77700","MOP 77700"],"award-info":[{"award-number":["MOP 77700","MOP 77700","MOP 77700","MOP 77700"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Rheumatoid arthritis (RA) is typically preceded by an extended preclinical period where circulating autoantibodies, particularly anti-citrullinated protein antibodies (ACPA), are detectable in the absence of clinical arthritis. Increased dietary intake of anti-inflammatory omega-3 (\u03c93) polyunsaturated fatty acids (PUFA) has been shown to be associated with a lower the risk of developing incident RA in large epidemiological studies. It is currently not known how changes in fatty acid (FA) metabolism may impact on the progression towards RA in at-risk individuals. To begin to address this question, we profiled serum FAs and oxylipins in an established cohort of at-risk ACPA-positive first-degree relatives (FDR) of RA patients (<jats:italic>N<\/jats:italic>\u2009=\u200931), some of whom developed RA (<jats:italic>N<\/jats:italic>\u2009=\u20094), and compared their profile to ACPA-negative FDR from the same population (<jats:italic>N<\/jats:italic>\u2009=\u200910).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Gas chromatography (GC) was used for FA quantitation. Oxylipins were extracted and quantified using high-performance liquid chromatography\u2013tandem mass spectrometry (HPLC\/MS\/MS).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Although we did not detect any meaningful differences in overall FA content between ACPA\u2009+\u2009and ACPA\u2009\u2212\u2009FDR, the levels of oxylipins derived from FA metabolism demonstrated significant differences between the two groups, with the ACPA\u2009+\u2009group demonstrating enrichment in circulating arachidonic acid- and eicosapentaenoic acid-derived molecules. Compared with the ACPA\u2009\u2212\u2009FDR group, the ACPA\u2009+\u2009FDR, including those who progressed into inflammatory arthritis, displayed higher levels of LOX-derived oxylipins.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>ACPA seropositivity in otherwise unaffected individuals at-risk for developing future RA based on family history (FDR) is associated with alterations in the serum oxylipin profile that suggests dysregulated LOX activity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-024-03274-0","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T07:02:50Z","timestamp":1707980570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lipoxygenase-derived oxylipins are enriched in anti-citrullinated protein antibody (ACPA)-positive individuals at risk for developing rheumatoid arthritis"],"prefix":"10.1186","volume":"26","author":[{"given":"Liam J.","family":"O\u2019Neil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidyanand","family":"Anaparti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Smolik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold M.","family":"Aukema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hani","family":"El-Gabalawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"issue":"13","key":"3274_CR1","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","volume":"320","author":"D Aletaha","year":"2018","unstructured":"Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360\u201372.","journal-title":"JAMA"},{"issue":"9","key":"3274_CR2","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1002\/art.40880","volume":"71","author":"S Tanner","year":"2019","unstructured":"Tanner S, Dufault B, Smolik I, Meng X, Anaparti V, Hitchon C, et al. A prospective study of the development of inflammatory arthritis in the family members of Indigenous North American people with rheumatoid arthritis. Arthritis Rheumatol. 2019;71(9):1494\u2013503.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"3274_CR3","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1136\/ard.2008.105759","volume":"69","author":"WH Bos","year":"2010","unstructured":"Bos WH, Wolbink GJ, Boers M, Tijhuis GJ, de Vries N, van der Horst-Bruinsma IE, et al. Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann Rheum Dis. 2010;69(3):490\u20134.","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"3274_CR4","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3945\/an.114.007732","volume":"6","author":"M Gabbs","year":"2015","unstructured":"Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr. 2015;6(5):513\u201340.","journal-title":"Adv Nutr"},{"issue":"1","key":"3274_CR5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12891-018-2381-3","volume":"20","author":"JA Sparks","year":"2019","unstructured":"Sparks JA, O\u2019Reilly EJ, Barbhaiya M, Tedeschi SK, Malspeis S, Lu B, et al. Association of fish intake and smoking with risk of rheumatoid arthritis and age of onset: a prospective cohort study. BMC Musculoskelet Disord. 2019;20(1):2.","journal-title":"BMC Musculoskelet Disord"},{"issue":"3","key":"3274_CR6","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1002\/art.41537","volume":"73","author":"J Rodriguez-Carrio","year":"2021","unstructured":"Rodriguez-Carrio J, Coras R, Alperi-Lopez M, Lopez P, Ulloa C, Ballina-Garcia FJ, et al. Profiling of serum oxylipins during the earliest stages of rheumatoid arthritis. Arthritis Rheumatol. 2021;73(3):401\u201313.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"3274_CR7","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3899\/jrheum.210614","volume":"49","author":"D Wiens","year":"2022","unstructured":"Wiens D, Smolik I, Meng X, Anaparti V, El-Gabalawy HS, O\u2019Neil LJ. Functional disability to evaluate the risk of arthritis in first-degree relatives of patients with rheumatoid arthritis. 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Usefulness of serum unbound free fatty acid levels to predict death early in patients with ST-segment elevation myocardial infarction (from the Thrombolysis In Myocardial Infarction [TIMI] II trial). Am J Cardiol. 2014;113(2):279\u201384.","journal-title":"Am J Cardiol"},{"key":"3274_CR14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.plefa.2016.09.007","volume":"115","author":"Z Bystricka","year":"2016","unstructured":"Bystricka Z, Durackova Z. Gas chromatography determination of fatty acids in the human erythrocyte membranes - a review. Prostaglandins Leukot Essent Fatty Acids. 2016;115:35\u201340.","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"3274_CR15","doi-asserted-by":"publisher","first-page":"102211","DOI":"10.1016\/j.plefa.2020.102211","volume":"163","author":"BK Lozier","year":"2020","unstructured":"Lozier BK, Kim RN, Zuromski LM, Kish-Trier E, De Biase I, Yuzyuk T. Effect of fasting status and other pre-analytical variables on quantitation of long-chain fatty acids in red blood cells. 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The Biomedical Research Ethics Board of the University of Manitoba approved the overall design of the study and consent forms (Ethics: 2005:093, Protocol: HS14453). The conduct of the study was guided by the principles of Community Based Participatory Research, a cornerstone of the Canadian Institutes of Health Research guidelines for Aboriginal health research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"51"}}