{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:34:06Z","timestamp":1791938046064,"version":"4.3.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Cerrahpasa Society of Rheumatology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Familial Mediterranean fever (FMF) is characterized by inflammatory attacks due to overactivation of pyrin inflammasome. This study aimed to investigate the reliability of S100A8\/A9, neopterin, and matrix metalloproteinase 3 (MMP3) at monitoring subclinical inflammation and disease activity, and at differentiating FMF attacks from appendicitis, the most common misdiagnosis among FMF patients. Blood samples (n\u2005=\u200575), comprising from FMF patients during an attack (n\u2005=\u200520), the same FMF patients during the attack-free period (n\u2005=\u200514), patients with appendicitis (n\u2005=\u200524), and healthy volunteers (n\u2005=\u200517) were obtained. Duplicate determinations of S100A8\/A9, neopterin, and MMP-3 levels were conducted using the enzyme-linked immunosorbent assay (ELISA). FMF patients with and without attack and patients with appendicitis had significantly elevated S100A8\/A9 levels compared to healthy volunteers (P-values:\u2005&amp;lt;\u20050.001, 0.036, 0.002, respectively). Patients with appendicitis and FMF patients with and without attack had significantly increased serum neopterin levels compared to healthy volunteers (P-value:\u2005&amp;lt;\u20050.001). MMP3 levels were significantly higher among patients with appendicitis and FMF patients during attack compared to healthy controls (P-values:\u2005&amp;lt;\u20050.001, 0.001). Serum levels of S100A8\/A9, neopterin, and MMP3 were increased significantly during attacks compared to attack-free periods among FMF patients (P-values: 0.03, 0.047, 0.007). S100A8\/A9 emerges as a valuable marker for monitoring disease activity. Neopterin and S100A8\/A9 might help physicians to monitor subclinical inflammation during the attack-free periods of FMF patients. MMP3 might aid in diagnosing FMF attacks when distinguishing between attack and attack-free periods is challenging.<\/jats:p>","DOI":"10.1093\/cei\/uxae049","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T11:42:06Z","timestamp":1718192526000},"page":"93-100","source":"Crossref","is-referenced-by-count":2,"title":["Exploring S100A8\/A9, neopterin, and MMP3 in familial Mediterranean fever"],"prefix":"10.1093","volume":"218","author":[{"given":"Ozgur C","family":"Kilinc","sequence":"first","affiliation":[{"name":"Istanbul University-Cerrahpasa Division of Rheumatology, Department of Internal Medicine, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonca S","family":"Akdeniz","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa Department of Emergency Medicine, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuleyha","family":"Taskin","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa Division of Rheumatology, Department of Internal Medicine, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Karabulut","sequence":"additional","affiliation":[{"name":"Bakirkoy Dr. Sadi Konuk Education and Research Hospital Department of General Surgery, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Kaya","sequence":"additional","affiliation":[{"name":"Bakirkoy Dr. Sadi Konuk Education and Research Hospital Department of General Surgery, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Murat","family":"Bolay\u0131rl\u0131","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa Department of Biochemistry, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunay","family":"Can","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa Department of Public Health Sciences, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9561-2282","authenticated-orcid":false,"given":"Serdal","family":"Ugurlu","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa Division of Rheumatology, Department of Internal Medicine, , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"2024091614535431700_CIT0001","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1016\/j.lpm.2018.08.014","article-title":"Familial Mediterranean fever","volume":"48","author":"Ozdogan","year":"2019","journal-title":"Presse Med"},{"key":"2024091614535431700_CIT0002","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/GIM.0b013e3182060456","article-title":"Familial Mediterranean fever--a review","volume":"13","author":"Shohat","year":"2011","journal-title":"Genet Med"},{"key":"2024091614535431700_CIT0003","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/ni.3457","article-title":"Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS","volume":"17","author":"Park","year":"2016","journal-title":"Nat Immunol"},{"key":"2024091614535431700_CIT0004","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S1097-2765(03)00056-X","article-title":"Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis","volume":"11","author":"Chae","year":"2003","journal-title":"Mol Cell"},{"key":"2024091614535431700_CIT0005","doi-asserted-by":"crossref","first-page":"9584","DOI":"10.3390\/ijms24119584","article-title":"An update on familial Mediterranean fever","volume":"24","author":"Lancieri","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2024091614535431700_CIT0006","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/rheumatology\/keaa378","article-title":"Predictors of persistent inflammation in familial Mediterranean fever and association with damage","volume":"60","author":"Babaoglu","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"2024091614535431700_CIT0007","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.3389\/fimmu.2018.02422","article-title":"Dynamics of inflammatory response in autoinflammatory disorders: autonomous and hyperinflammatory states","volume":"9","author":"Gul","year":"2018","journal-title":"Front Immunol"},{"key":"2024091614535431700_CIT0008","first-page":"119","article-title":"Familial Mediterranean fever: misdiagnosis and diagnostic delay in Turkey","volume":"37","author":"Erdogan","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"2024091614535431700_CIT0009","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3390\/cells11020236","article-title":"S100A8\/A9 is a marker for the release of neutrophil extracellular traps and induces neutrophil activation","volume":"11","author":"Sprenkeler","year":"2022","journal-title":"Cells"},{"key":"2024091614535431700_CIT0010","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.3389\/fimmu.2018.01298","article-title":"S100A8\/A9 in inflammation","volume":"9","author":"Wang","year":"2018","journal-title":"Front Immunol"},{"key":"2024091614535431700_CIT0011","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pharmthera.2016.07.015","article-title":"S100A8\/A9: from basic science to clinical application","volume":"167","author":"Pruenster","year":"2016","journal-title":"Pharmacol Ther"},{"key":"2024091614535431700_CIT0012","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.3390\/antiox12051037","article-title":"Tetrahydrobiopterin: beyond its traditional role as a cofactor","volume":"12","author":"Eichwald","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"2024091614535431700_CIT0013","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00011-003-1181-9","article-title":"Potential role of immune system activation-associated production of neopterin derivatives in humans","volume":"52","author":"Hoffmann","year":"2003","journal-title":"Inflamm Res"},{"key":"2024091614535431700_CIT0014","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/art.1780330211","article-title":"Ligand-dependent release of active neutrophil collagenase","volume":"33","author":"Chatham","year":"1990","journal-title":"Arthritis Rheum"},{"key":"2024091614535431700_CIT0015","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1021\/acsbiomaterials.9b00084","article-title":"Fluorogenic Probe for Detecting Active Matrix Metalloproteinase-3 (MMP-3) in Plasma and Peripheral Blood Neutrophils to Indicate the Severity of Rheumatoid Arthritis","volume":"5","author":"Lee","year":"2019","journal-title":"ACS Biomater Sci Eng"},{"key":"2024091614535431700_CIT0016","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1038\/s41598-020-61094-z","article-title":"Calprotectin, a new biomarker for diagnosis of acute respiratory infections","volume":"10","author":"Havelka","year":"2020","journal-title":"Sci Rep"},{"key":"2024091614535431700_CIT0017","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.1038\/s41598-020-62388-y","article-title":"Validation of calprotectin as a novel biomarker for the diagnosis of pleural effusion: a multicentre trial","volume":"10","author":"Botana-Rial","year":"2020","journal-title":"Sci Rep"},{"key":"2024091614535431700_CIT0018","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1136\/annrheumdis-2014-205958","article-title":"Neutrophil extracellular traps regulate IL-1beta-mediated inflammation in familial Mediterranean fever","volume":"75","author":"Apostolidou","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2024091614535431700_CIT0019","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.3906\/sag-2008-11","article-title":"Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review","volume":"50","author":"Tufan","year":"2020","journal-title":"Turk J Med Sci"},{"key":"2024091614535431700_CIT0020","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jaci.2023.01.037","article-title":"Complex regulation of alarmins S100A8\/A9 and secretion via gasdermin D pores exacerbates autoinflammation in familial Mediterranean fever","volume":"152","author":"Jorch","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"2024091614535431700_CIT0021","doi-asserted-by":"crossref","first-page":"553911","DOI":"10.3389\/fimmu.2021.553911","article-title":"Immune Resolution Dilemma: Host Antimicrobial Factor S100A8\/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis","volume":"12","author":"Shankar","year":"2021","journal-title":"Front Immunol"},{"key":"2024091614535431700_CIT0022","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/acem.12160","article-title":"Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis","volume":"20","author":"Schellekens","year":"2013","journal-title":"Acad Emerg Med"},{"key":"2024091614535431700_CIT0023","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ajem.2016.02.011","article-title":"Usefulness of new and traditional serum biomarkers in children with suspected appendicitis","volume":"34","author":"Benito","year":"2016","journal-title":"Am J Emerg Med"},{"key":"2024091614535431700_CIT0024","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1553-2712.2011.01251.x","article-title":"Novel serum and urine markers for pediatric appendicitis","volume":"19","author":"Kharbanda","year":"2012","journal-title":"Acad Emerg Med"},{"key":"2024091614535431700_CIT0025","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":"2024091614535431700_CIT0026","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1007\/s11845-022-03173-w","article-title":"Assessment of serum neopterin and calprotectin as biomarkers for subclinical inflammation in patients with familial Mediterranean fever","volume":"192","author":"Tezcan","year":"2023","journal-title":"Ir J Med Sci"},{"key":"2024091614535431700_CIT0027","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.3346\/jkms.2020.35.e63","article-title":"Can calprotectin show subclinical inflammation in familial Mediterranean fever patients?","volume":"35","author":"Asan","year":"2020","journal-title":"J Korean Med Sci"},{"key":"2024091614535431700_CIT0028","doi-asserted-by":"crossref","first-page":"322","DOI":"10.31138\/mjr.33.3.322","article-title":"Assessment of serum resistin and plasma calprotectin levels as biomarkers of inflammation in patients with familial Mediterranean fever disease","volume":"33","author":"Kilicaslan","year":"2022","journal-title":"Mediterr J Rheumatol"},{"key":"2024091614535431700_CIT0029","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jbspin.2004.03.011","article-title":"Interferon-gamma levels in familial Mediterranean fever","volume":"72","author":"Koklu","year":"2005","journal-title":"Joint Bone Spine"},{"key":"2024091614535431700_CIT0030","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0014-5793(96)00729-6","article-title":"Neopterin activates transcription factor nuclear factor-kappa B in vascular smooth muscle cells","volume":"391","author":"Hoffmann","year":"1996","journal-title":"FEBS Lett"},{"key":"2024091614535431700_CIT0031","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/aid.1997.13.173","article-title":"Trans-activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro","volume":"13","author":"Baier-Bitterlich","year":"1997","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2024091614535431700_CIT0032","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1046\/j.1365-2249.1999.01071.x","article-title":"Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells","volume":"118","author":"Hoffmann","year":"1999","journal-title":"Clin Exp Immunol"},{"key":"2024091614535431700_CIT0033","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3109\/s10165-011-0517-5","article-title":"Acute phase response and oxidative stress status in familial Mediterranean fever (FMF)","volume":"22","author":"Guzel","year":"2012","journal-title":"Mod Rheumatol"},{"key":"2024091614535431700_CIT0034","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1001\/archsurg.1995.01430120068010","article-title":"Inflammatory response in peritoneal exudate and plasma of patients undergoing planned relaparotomy for severe secondary peritonitis","volume":"130","author":"Holzheimer","year":"1995","journal-title":"Arch Surg"},{"key":"2024091614535431700_CIT0035","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3390\/cells10020280","article-title":"Modulatory impact of adipose-derived mesenchymal stem cells of ankylosing spondylitis patients on T helper cell differentiation","volume":"10","author":"Kuca-Warnawin","year":"2021","journal-title":"Cells"},{"key":"2024091614535431700_CIT0036","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/cells9020482","article-title":"T helper cells: the modulators of inflammation in multiple sclerosis","volume":"9","author":"Kunkl","year":"2020","journal-title":"Cells"},{"key":"2024091614535431700_CIT0037","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00296-019-04391-9","article-title":"Evaluation of co-existing diseases in children with familial Mediterranean fever","volume":"40","author":"Yildiz","year":"2020","journal-title":"Rheumatol Int"},{"key":"2024091614535431700_CIT0038","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1136\/ard.2003.007013","article-title":"Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever","volume":"63","author":"Sackesen","year":"2004","journal-title":"Ann Rheum Dis"},{"key":"2024091614535431700_CIT0039","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1183\/09031936.05.00021304","article-title":"Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice","volume":"25","author":"Irifune","year":"2005","journal-title":"Eur Respir J"},{"key":"2024091614535431700_CIT0040","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.4049\/jimmunol.166.3.1471","article-title":"Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-gamma-dependent mechanism","volume":"166","author":"Tang","year":"2001","journal-title":"J Immunol"},{"key":"2024091614535431700_CIT0041","first-page":"2011","article-title":"Th1 polarization in familial Mediterranean fever","volume":"30","author":"Aypar","year":"2003","journal-title":"J Rheumatol"},{"key":"2024091614535431700_CIT0042","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.yexmp.2007.04.003","article-title":"Matrix metalloproteinase-3 (stromelysin-1) in acute inflammatory tissue injury","volume":"83","author":"Nerusu","year":"2007","journal-title":"Exp Mol Pathol"},{"key":"2024091614535431700_CIT0043","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0014-5793(89)80657-X","article-title":"Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (\u2018gelatinase\u2019) by human neutrophil elastase and cathepsin G","volume":"249","author":"Okada","year":"1989","journal-title":"FEBS Lett"},{"key":"2024091614535431700_CIT0044","doi-asserted-by":"crossref","first-page":"16300","DOI":"10.1016\/S0021-9258(18)49254-X","article-title":"Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by dexamethasone","volume":"262","author":"Frisch","year":"1987","journal-title":"J Biol Chem"},{"key":"2024091614535431700_CIT0045","doi-asserted-by":"crossref","first-page":"17238","DOI":"10.1016\/S0021-9258(17)44894-0","article-title":"Discoordinate expression of stromelysin, collagenase, and tissue inhibitor of metalloproteinases-1 in rheumatoid human synovial fibroblasts. Synergistic effects of interleukin-1 and tumor necrosis factor-alpha on stromelysin expression","volume":"265","author":"MacNaul","year":"1990","journal-title":"J Biol Chem"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxae049\/58657189\/uxae049.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/218\/1\/93\/59140863\/uxae049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/218\/1\/93\/59140863\/uxae049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T14:54:33Z","timestamp":1726498473000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/218\/1\/93\/7691594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,6,12]]},"published-print":{"date-parts":[[2024,9,16]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxae049","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,6,12]]}}}