{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:55:15Z","timestamp":1781769315046,"version":"3.54.5"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Research Centre Egypt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial Mediterranean Fever (FMF) is a chronic autoinflammatory illness that follows a pattern of periodic attacks; however, the majority of cases experience ongoing subclinical inflammation during the attack-free periods that could lead to the development of anemia, splenomegaly, heart disease, and the major complication, amyloidosis. Midkine\/Pleiotrophin (MDK\/PTN) are heparin-binding cytokines, with upregulated expression in various inflammatory and malignant diseases. Thus, the present research aims to identify the role of MDK and PTN in the pathogenesis of chronic inflammation and to explore the potential of both cytokines as new markers of subclinical inflammation in FMF. Blood samples from 30 FMF patients and 30 controls were collected to assess gene expression and protein levels of MDK and PTN by qRT-PCR and ELISA, respectively. Statistical correlation between different parameters and bioinformatic analysis to link the\n                    <jats:italic>MEFV<\/jats:italic>\n                    gene to the relevant genes was also performed. The expression of MDK and PTN genes was significantly higher in FMF children than in healthy subjects. Additionally, the serum level of MDK showed a fourfold increase in patients compared to controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The levels of PTN were also higher in cases, but without reaching the significance level (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.096). MDK gene expression was inversely related to ESR level and positively correlated to serum level of MDK and anemia occurrence.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    : Collectively, our results disclosed that Midkine could be identified as a useful clinical tool in diagnosing and managing systemic and subclinical inflammation in FMF cases, while Pleiotrophin might provide additional information on acute inflammatory processes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td align=\"left\" colspan=\"2\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                              \u2022\u00a0\n                              <jats:italic>Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent bouts of\u00a0systemic and acute inflammation.<\/jats:italic>\n                              \u2022\u00a0\n                              <jats:italic>Midkine and Pleiotrophin are heparin-binding growth factors often associated with inflammatory responses.<\/jats:italic>\n                              <jats:bold>What is New:<\/jats:bold>\n                              \u2022\u00a0\n                              <jats:italic>Midkine could be identified as a reliable clinical biomarker for both diagnosing and managing systemic and\u00a0subclinical inflammatory phase in FMF patients.<\/jats:italic>\n                              \u2022\u00a0\n                              <jats:italic>Pleiotrophin might provide additional information on acute inflammatory processes.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-06981-9","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:10:58Z","timestamp":1779084658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence of the role of Midkine and Pleiotrophin in the pathogenesis of Familial Mediterranean Fever"],"prefix":"10.1007","volume":"185","author":[{"given":"Zeinab Y.","family":"Abdallah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada Nour","family":"Eldeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona F.","family":"Sokkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania Fawzy Mahmoud","family":"abdelkawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa S.","family":"Lotfy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shymaa H.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala T.","family":"El-Bassyouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"6981_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13052-019-0766-z","volume":"46","author":"MC Maggio","year":"2020","unstructured":"Maggio MC, Corsello G (2020) FMF is not always \u201cfever\u201d: from clinical presentation to \u201ctreat to target.\u201d Ital J Pediatr 46:7","journal-title":"Ital J Pediatr"},{"key":"6981_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fped.2021.805919","volume":"9","author":"K \u00d6zt\u00fcrk","year":"2022","unstructured":"\u00d6zt\u00fcrk K, Co\u015fkuner T, Baglan E, S\u00f6nmez HE, Yener GO, \u00c7akmak F et al (2022) Real-life data from the largest pediatric Familial Mediterranean Fever cohort. 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