{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T18:01:03Z","timestamp":1781287263797,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003559","name":"Ministry of National Defense","doi-asserted-by":"publisher","award":["MND\u2010MAB\u2010110\u2010127"],"award-info":[{"award-number":["MND\u2010MAB\u2010110\u2010127"]}],"id":[{"id":"10.13039\/501100003559","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003559","name":"Ministry of National Defense","doi-asserted-by":"publisher","award":["MND\u2010MAB\u2010110\u2010124"],"award-info":[{"award-number":["MND\u2010MAB\u2010110\u2010124"]}],"id":[{"id":"10.13039\/501100003559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site\u2010specific complementary diagnostic markers for periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme\u2010linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut\u2010off point, area under the ROC curve, sensitivity, and specificity were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b\u2009+\u2009C4b in the GT can significantly differentiate the disease status at the tissue level (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Similarly, the expression levels of C3b\u2009+\u2009C4b in GCF can statistically distinguish periodontitis sites from healthy ones (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site\u2010specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13164","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T11:39:42Z","timestamp":1689680382000},"page":"1020-1030","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complement components C3b and C4b as potential reliable site\u2010specific diagnostic biomarkers for periodontitis"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-8828","authenticated-orcid":false,"given":"Ren\u2010Yeong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Periodontology School of Dentistry, Tri\u2010Service General Hospital and National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010Yi","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry, Tri\u2010Service General Hospital and National Defense Medical Center  Taipei Taiwan"},{"name":"Graduate Institute of Dental Sciences National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Dan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry, Tri\u2010Service General Hospital and National Defense Medical Center  Taipei Taiwan"},{"name":"Graduate Institute of Dental Sciences National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0568-124X","authenticated-orcid":false,"given":"Thomas E","family":"Van\u00a0Dyke","sequence":"additional","affiliation":[{"name":"Department of Applied Oral Sciences The Forsyth Institute  Cambridge Massachusetts USA"},{"name":"Oral Medicine, Infection, and Immunity Harvard School of Dental Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010En","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry, Tri\u2010Service General Hospital and National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhong\u2010Jhe","family":"You","sequence":"additional","affiliation":[{"name":"AP Biosciences, Inc.  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