{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:05:40Z","timestamp":1784005540343,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate diagnosis of periprosthetic joint infection (PJI) is critical yet challenging. The role of autoantibodies in PJI remains largely unexplored. In this study, we employed phage display immunoprecipitation sequencing (PhIP-Seq) to profile PJI-associated autoantibodies and assess their diagnostic utility in PJI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected plasma samples from a cohort of 45 patients, including 25 with PJI, 9 with aseptic loosening, and 11 post-primary arthroplasty without complications. Initially, PhIP-Seq screening was performed on 10 samples (five PJI and five post-primary arthroplasty) to identify significantly differentially expressed autoantibodies. Subsequently, the immunoglobulin G (IgG) levels of these specific autoantibodies were quantified in the plasma of all participants via ELISA, and statistical analysis was performed to evaluate their diagnostic performance in PJI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PhIP-Seq identified IFT80 and VPS54 as PJI-associated autoantigens. ELISA confirmed significantly elevated levels of corresponding IgG antibodies in PJI patients compared to those with aseptic loosening or post-primary arthroplasty (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). Both autoantibodies demonstrated preliminary diagnostic performance: IFT80 achieved an area under the curve (AUC) of 0.797 (sensitivity = 56.0%, specificity = 95.0%), while VPS54 yielded an AUC of 0.776 (sensitivity = 72.0%, specificity = 75.0%). A combined diagnostic model integrating both biomarkers further enhanced the diagnostic performance (AUC = 0.810, sensitivity = 68.0%, specificity = 80.0%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes IFT80 and VPS54 as novel autoantibodies in PJI. Their corresponding autoantibodies exhibit robust diagnostic potential, offering support for the development of serological assays to improve PJI diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1824616","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:21:58Z","timestamp":1784002918000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of autoantibody markers based on phage display immunoprecipitation sequencing technology in the diagnosis of periprosthetic joint infections"],"prefix":"10.3389","volume":"16","author":[{"given":"GangJie","family":"Chang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YangCheng","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianZhong","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12122958","article-title":"Role of biomarkers in periprosthetic joint infections","volume":"12","author":"Akcaalan","year":"2022","journal-title":"Diagnostics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1016\/j.immuni.2023.04.003","article-title":"Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire","volume":"56","author":"Andreu-S\u00e1nchez","year":"2023","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1002\/ksa.12419","article-title":"Weight\u2010bearing pain and implant migration, progressive radiolucencies, radiolucency more than 2 mm and subsidence on radiographs and CT are generally accepted criteria for knee arthroplasty loosening: An international delphi consensus study","volume":"33","author":"Buijs","year":"2025","journal-title":"Knee Surg. Sports Traumatol Arthrosc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/20552076241253531","article-title":"A machine learning-based model for \u201cin-time\u201d prediction of periprosthetic joint infection","volume":"10","author":"Chen","year":"2024","journal-title":"DIG Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/00220345211046606","article-title":"Role of primary cilia in bone and cartilage","volume":"101","author":"Chinipardaz","year":"2022","journal-title":"J. Dent Res."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2201490119","article-title":"IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation","volume":"119","author":"Deepak","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12101492","article-title":"A narrative review on the role of dalbavancin in the treatment of bone and joint infections","volume":"12","author":"Dimopoulou","year":"2023","journal-title":"Antibiotics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/s44161-024-00525-w","article-title":"An engineered human cardiac tissue model reveals contributions of systemic lupus erythematosus autoantibodies to myocardial injury","volume":"3","author":"Fleischer","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1051\/sicotj\/2021060","article-title":"Prevention of early complications following total hip replacement","volume":"7","author":"Fontalis","year":"2021","journal-title":"SICOT-J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1186\/s12891-019-2941-1","article-title":"Diagnostic criteria of periprosthetic joint infection: A prospective study protocol to validate the feasibility of the 2018 new definition for Chinese patients","volume":"20","author":"Guan","year":"2019","journal-title":"BMC Musculoskelet. Disord."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3672","DOI":"10.1007\/s00167-022-07196-9","article-title":"Higher sensitivity and accuracy of synovial next\u2010generation sequencing in comparison to culture in diagnosing periprosthetic joint infection: A systematic review and meta\u2010analysis","volume":"31","author":"Hantouly","year":"2023","journal-title":"Knee Surg. Sports Traumatol Arthrosc"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fbinf.2024.1424202","article-title":"PhIP-seq: Methods, applications and challenges","volume":"4","author":"Huang","year":"2024","journal-title":"Front. Bioinform."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0319509","article-title":"Coping with chronic periprosthetic joint infection after failed revision of total knee and hip arthroplasty: A qualitative study on patient\u2019s experiences in treatment and healing","volume":"20","author":"Krenn","year":"2025","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","first-page":"780","DOI":"10.2106\/JBJS.F.00222","article-title":"Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030: The Journal of Bone & Joint Surgery","volume":"89","author":"Kurtz","year":"2007","journal-title":"J. Bone Joint Surg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s42003-020-0767-x","article-title":"Primary cilia control cell alignment and patterning in bone development via ceramide-PKC\u03b6-\u03b2-catenin signaling","volume":"3","author":"Lim","year":"2020","journal-title":"Commun. Biol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1564488","article-title":"Comprehensive analysis of culture-negative periprosthetic joint infection with metagenomic next-generation sequencing","volume":"15","author":"Lin","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14726","article-title":"The application of topical antibiotics for the prevention of infections in primary joint arthroplasty. An umbrella review of systematic reviews and meta\u2010analysis","volume":"21","author":"Luo","year":"2024","journal-title":"Int. Wound J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1302\/0301-620X.103B1.BJJ-2020-1381.R1","article-title":"The EBJIS definition of periprosthetic joint infection: A practical guide for clinicians","author":"McNally","year":"2021","journal-title":"Bone Joint J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"629","DOI":"10.5312\/wjo.v12.i9.629","article-title":"Hip prosthetic loosening: A very personal review","volume":"12","author":"Mj\u00f6berg","year":"2021","journal-title":"WJO"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1038\/s41596-018-0025-6","article-title":"PhIP-seq characterization of serum antibodies using oligonucleotide-encoded peptidomes","volume":"13","author":"Mohan","year":"2018","journal-title":"Nat. Protoc."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13195716","article-title":"Role of serum biomarkers in differentiating periprosthetic joint infections from aseptic failures after total hip arthroplasties","volume":"13","author":"Moldovan","year":"2024","journal-title":"JCM"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1482728","article-title":"Autoimmune disease: A view of epigenetics and therapeutic targeting","volume":"15","author":"Mu","year":"2024","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/jb\/mvi024","article-title":"Multi-component protein complexes and golgi membrane trafficking","volume":"137","author":"Oka","year":"2005","journal-title":"J. Biochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s12306-021-00734-7","article-title":"Management of prosthetic joint infections: A guidelines comparison","volume":"106","author":"Ometti","year":"2022","journal-title":"Musculoskelet. Surg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/cis803","article-title":"Diagnosis and management of prosthetic joint infection: Clinical practice guidelines by the infectious diseases society of Americaa","volume":"56","author":"Osmon","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/jid.2011.347","article-title":"Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity","volume":"132","author":"Paek","year":"2012","journal-title":"J. Invest Dermatol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"469","DOI":"10.5483\/BMBRep.2023-0114","article-title":"Scarring the early-life microbiome: Its potential life-long effects on human health and diseases","volume":"56","author":"Park","year":"2023","journal-title":"BMB Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"246","DOI":"10.5483\/BMBRep.2021.54.5.270","article-title":"The golgi complex: A hub of the secretory pathway","volume":"54","author":"Park","year":"2021","journal-title":"BMB Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/j.arth.2014.03.009","article-title":"Definition of periprosthetic joint infection","volume":"29","author":"Parvizi","year":"2014","journal-title":"J. Arthroplasty"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1242\/bio.053421","article-title":"Vps54 regulates Drosophila neuromuscular junction development and interacts genetically with Rab7 to control composition of the postsynaptic density","volume":"9","author":"Patel","year":"2020","journal-title":"Biol. Open"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1007\/s00264-017-3430-5","article-title":"C-reactive protein may misdiagnose prosthetic joint infections, particularly chronic and low-grade infections","volume":"41","author":"P\u00e9rez-Prieto","year":"2017","journal-title":"Int. Orthopaedics (SICOT)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"5251","DOI":"10.1128\/MCB.00495-09","article-title":"Dual Roles of the Mammalian GARP Complex in Tethering and SNARE Complex Assembly at the trans -Golgi Network","volume":"29","author":"P\u00e9rez-Victoria","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.174976","article-title":"Validation of a murine proteome-wide phage display library for identification of autoantibody specificities","volume":"8","author":"Rackaityte","year":"2023","journal-title":"JCI Insight"},{"key":"B34","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/s42003-025-08143-3","article-title":"The role of PD-1\/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections","volume":"8","author":"Ren","year":"2025","journal-title":"Commun. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1093\/hmg\/ddr013","article-title":"An Ift80 mouse model of short rib polydactyly syndromes shows defects in hedgehog signalling without loss or malformation of cilia","volume":"20","author":"Rix","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9091128","article-title":"Serum inflammatory biomarkers in the diagnosis of periprosthetic joint infections","volume":"9","author":"Sigmund","year":"2021","journal-title":"Biomedicines"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11050568","article-title":"Phage ImmunoPrecipitation sequencing (PhIP-seq): The promise of high throughput serology","volume":"11","author":"Tiu","year":"2022","journal-title":"Pathogens"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156159","article-title":"IFT80 and TRPA1 cooperatively regulate bone formation by calcium signaling in response to mechanical stimuli","volume":"166","author":"Wang","year":"2025","journal-title":"Metabolism"},{"key":"B39","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.arth.2022.12.010","article-title":"D-dimer, erythrocyte sedimentation rate, and C-reactive protein sensitivities for periprosthetic joint infection diagnosis","volume":"38","author":"Wixted","year":"2023","journal-title":"J. Arthroplasty"},{"key":"B40","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s10195-022-00657-4","article-title":"C-reactive protein (CRP)\/albumin-to-globulin ratio (AGR) is a valuable test for diagnosing periprosthetic joint infection: A single-center retrospective study","volume":"23","author":"Wu","year":"2022","journal-title":"J. Orthop. Traumatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1097\/CM9.0000000000002215","article-title":"Combination of C-reactive protein and fibrinogen is useful for diagnosing periprosthetic joint infection in patients with inflammatory diseases","volume":"135","author":"Xu","year":"2022","journal-title":"Chin. Med. J."},{"key":"B42","doi-asserted-by":"publisher","first-page":"155","DOI":"10.5792\/ksrr.16.034","article-title":"A review of the literature on culture-negative periprosthetic joint infection: Epidemiology, diagnosis and treatment","volume":"29","author":"Yoon","year":"2017","journal-title":"Knee Surg. Relat. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.7150\/ijbs.27231","article-title":"Ciliary IFT80 regulates dental pulp stem cells differentiation by FGF\/FGFR1 and hh\/BMP2 signaling","volume":"15","author":"Yuan","year":"2019","journal-title":"Int. J. Biol. Sci."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1824616\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:21:59Z","timestamp":1784002919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1824616\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":43,"alternative-id":["10.3389\/fcimb.2026.1824616"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1824616","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"article-number":"1824616"}}