{"doi":"10.1053/j.gastro.2025.08.040","title":"Fecal Detection of Calprotectin Subunits Links Inflammatory Bowel Disease Activity With Chronicity of Intestinal Inflammation","abstract":"BACKGROUND & AIMS: Quantification of the human S100A8/S100A9 tetrameric protein complex in stool, referred to as fecal calprotectin, is an extensively validated biomarker supporting the diagnosis and management of gastrointestinal diseases. Here, we studied the quaternary protein structures (termed configuration) of S100A8 and S100A9 and their biological function in inflammatory bowel diseases (IBD). METHODS: We dissected fecal S100A8 and S100A9 configurations in patients with IBD by size-exclusion chromatography coupled with tandem mass spectrometry and systematically defined human S100A8 and S100A9 homodimer functions compared with the calprotectin heterotetramer (CP) in the intestine of mice and in human epithelium and T cells. Moreover, we report a protein interaction network of fecal S100A8 and S100A9 in IBD. RESULTS: T cells, which promoted experimental colitis. In turn, genetic inactivation of S100a9 protected against experimental enteritis and colitis, and pharmacologic inhibition of S100A9 ameliorated chronic colitis. CONCLUSIONS: Collectively, this study links the detection of fecal S100A9 dimers with clinical and endoscopic disease activity in IBD and identifies inflammatory actions of S100A8 and S100A9 homodimers in the intestine. Our findings pave the way for novel diagnostic and therapeutic approaches in patients with inflammatory diseases of the intestine.","journal":"Gastroenterology","year":2025,"id":535564,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9658,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1032981,"name":"Richard Hilbe","orcid":"0000-0001-9987-109X","position":1,"is_corresponding":false},{"id":1419644,"name":"Luis Zundel","orcid":null,"position":2,"is_corresponding":false},{"id":17140,"name":"Peter Willeit","orcid":"0000-0002-1866-7159","position":3,"is_corresponding":false},{"id":309065,"name":"Klaus Faserl","orcid":"0000-0003-1646-3256","position":4,"is_corresponding":false},{"id":668010,"name":"Christina Plattner","orcid":"0000-0002-3217-3278","position":5,"is_corresponding":false},{"id":1419185,"name":"Andreas Zollner","orcid":"0000-0001-6095-068X","position":6,"is_corresponding":false},{"id":1419645,"name":"Moritz Meyer","orcid":null,"position":7,"is_corresponding":false},{"id":1419186,"name":"Kerstin Siegmund","orcid":"0000-0002-3654-1170","position":8,"is_corresponding":false},{"id":1419187,"name":"Victoria Klepsch","orcid":"0000-0003-4146-4664","position":9,"is_corresponding":false},{"id":56549,"name":"Valentin Marteau","orcid":"0000-0002-3667-1653","position":10,"is_corresponding":false},{"id":348318,"name":"Arnau Vich Vila","orcid":"0000-0003-4691-5583","position":11,"is_corresponding":false},{"id":880644,"name":"Julian Schwärzler","orcid":"0000-0001-9939-7324","position":12,"is_corresponding":false},{"id":1419646,"name":"Kathrin Vouk","orcid":null,"position":13,"is_corresponding":false},{"id":1419647,"name":"A Kozsar","orcid":null,"position":14,"is_corresponding":false},{"id":722248,"name":"Dietmar Rieder","orcid":"0000-0003-1754-690X","position":15,"is_corresponding":false},{"id":1419648,"name":"A Weichberger","orcid":null,"position":16,"is_corresponding":false},{"id":1419188,"name":"Bettina Sarg","orcid":"0000-0002-4785-8739","position":17,"is_corresponding":false},{"id":1419189,"name":"Felix Grabherr","orcid":"0000-0001-5731-8253","position":18,"is_corresponding":false},{"id":1239338,"name":"Lisa Mayr","orcid":"0000-0003-0869-242X","position":19,"is_corresponding":false},{"id":1419649,"name":"Patrizia Moser","orcid":null,"position":20,"is_corresponding":false},{"id":56550,"name":"Niloofar Nemati","orcid":"0009-0004-5923-2073","position":21,"is_corresponding":false},{"id":230661,"name":"Sabine Scholl‐Bürgi","orcid":"0000-0002-2529-4231","position":22,"is_corresponding":false},{"id":230652,"name":"Daniela Karall","orcid":"0000-0002-4846-1047","position":23,"is_corresponding":false},{"id":736965,"name":"Georg F. Vogel","orcid":"0000-0002-2515-4490","position":24,"is_corresponding":false},{"id":262526,"name":"Lina Welz","orcid":"0009-0008-3779-623X","position":25,"is_corresponding":false},{"id":736964,"name":"Denise Aldrian","orcid":"0000-0002-6787-4939","position":26,"is_corresponding":false},{"id":1419650,"name":"Robert Koch","orcid":null,"position":27,"is_corresponding":false},{"id":1419651,"name":"Alexandra Pfister","orcid":null,"position":28,"is_corresponding":false},{"id":642932,"name":"Qitao Ran","orcid":"0000-0002-2127-8349","position":29,"is_corresponding":false},{"id":242958,"name":"Arthur Kaser","orcid":"0000-0003-1419-3344","position":30,"is_corresponding":false},{"id":581212,"name":"Richard S. Blumberg","orcid":"0000-0002-4622-825X","position":31,"is_corresponding":false},{"id":615407,"name":"Ivan Tancevski","orcid":"0000-0001-5116-8960","position":32,"is_corresponding":false},{"id":1021516,"name":"Felix Sommer","orcid":"0000-0002-6545-3487","position":33,"is_corresponding":false},{"id":28514,"name":"Petra Bächer","orcid":"0000-0003-4264-6451","position":34,"is_corresponding":false},{"id":14022,"name":"Stefan Schreiber","orcid":"0000-0003-2254-7771","position":35,"is_corresponding":false},{"id":14432,"name":"Philip Rosenstiel","orcid":"0000-0002-9692-8828","position":36,"is_corresponding":false},{"id":262521,"name":"Konrad Aden","orcid":"0000-0003-3482-7316","position":37,"is_corresponding":false},{"id":1419190,"name":"Gottfried Baier","orcid":"0000-0002-2085-8325","position":38,"is_corresponding":false},{"id":1419191,"name":"Latifa Bakiri","orcid":"0000-0002-6300-2420","position":39,"is_corresponding":false},{"id":672816,"name":"Thomas Müller","orcid":"0000-0001-8908-5589","position":40,"is_corresponding":false},{"id":851344,"name":"Günter Weiß","orcid":"0000-0003-0709-2158","position":41,"is_corresponding":false},{"id":1419652,"name":"Imke Atreya","orcid":null,"position":42,"is_corresponding":false},{"id":1269260,"name":"Raja Atreya","orcid":"0000-0002-8556-8433","position":43,"is_corresponding":false},{"id":857413,"name":"Christoph Becker","orcid":"0000-0002-1388-1041","position":44,"is_corresponding":false},{"id":1419653,"name":"Christian Bojarski","orcid":null,"position":45,"is_corresponding":false},{"id":1419654,"name":"Nathalie Britzen-Laurent","orcid":null,"position":46,"is_corresponding":false},{"id":1419655,"name":"Caroline Bosch-Voskens","orcid":null,"position":47,"is_corresponding":false},{"id":1419656,"name":"Hyun-Dong Chang","orcid":null,"position":48,"is_corresponding":false},{"id":28471,"name":"Andreas Diefenbach","orcid":"0000-0002-9176-9530","position":49,"is_corresponding":false},{"id":753680,"name":"Claudia Günther","orcid":"0000-0002-4330-1861","position":50,"is_corresponding":false},{"id":618096,"name":"Ahmed N. Hegazy","orcid":"0000-0002-2946-8251","position":51,"is_corresponding":false},{"id":1419657,"name":"Kai Hildner","orcid":null,"position":52,"is_corresponding":false},{"id":1419658,"name":"Christoph S.N. Klose","orcid":null,"position":53,"is_corresponding":false},{"id":1419659,"name":"Kristina Koop","orcid":null,"position":54,"is_corresponding":false},{"id":1419660,"name":"Susanne Krug","orcid":null,"position":55,"is_corresponding":false},{"id":991160,"name":"Anja A. Kühl","orcid":"0000-0003-2293-5387","position":56,"is_corresponding":false},{"id":1026693,"name":"Moritz Leppkes","orcid":"0000-0003-2311-090X","position":57,"is_corresponding":false},{"id":986351,"name":"Rocío López-Posadas","orcid":"0000-0002-2398-5864","position":58,"is_corresponding":false},{"id":1419661,"name":"Leif S.-H Ludwig","orcid":null,"position":59,"is_corresponding":false},{"id":635536,"name":"Clemens Neufert","orcid":null,"position":60,"is_corresponding":false},{"id":89161,"name":"Markus Neurath","orcid":null,"position":61,"is_corresponding":false},{"id":1419662,"name":"Jay Patankar","orcid":null,"position":62,"is_corresponding":false},{"id":1419663,"name":"Magdalena Prüß","orcid":null,"position":63,"is_corresponding":false},{"id":620169,"name":"Andreas Radbruch","orcid":"0000-0001-5753-0000","position":64,"is_corresponding":false},{"id":337031,"name":"Chiara Romagnani","orcid":"0000-0002-5167-7463","position":65,"is_corresponding":false},{"id":1419664,"name":"Francesca Ronchi","orcid":null,"position":66,"is_corresponding":false},{"id":813491,"name":"Ashley Sanders","orcid":"0000-0002-8834-5489","position":67,"is_corresponding":false},{"id":28441,"name":"Alexander Scheffold","orcid":"0000-0002-0626-343X","position":68,"is_corresponding":false},{"id":1419665,"name":"Jörg-Dieter Schulzke","orcid":null,"position":69,"is_corresponding":false},{"id":1419666,"name":"Michael Schumann","orcid":null,"position":70,"is_corresponding":false},{"id":1419667,"name":"Sebastian Schürmann","orcid":null,"position":71,"is_corresponding":false},{"id":78759,"name":"Britta Siegmund","orcid":"0000-0002-0055-958X","position":72,"is_corresponding":false},{"id":857414,"name":"Michael Stürzl","orcid":"0000-0002-9276-2824","position":73,"is_corresponding":false},{"id":1419668,"name":"Antigoni Triantafyllopoulou","orcid":null,"position":74,"is_corresponding":false},{"id":1419669,"name":"Maximilian Waldner","orcid":null,"position":75,"is_corresponding":false},{"id":78755,"name":"Carl Weidinger","orcid":"0000-0002-9948-0088","position":76,"is_corresponding":false},{"id":625803,"name":"Stefan Wirtz","orcid":"0000-0001-6936-7431","position":77,"is_corresponding":false},{"id":1419670,"name":"Sebastian Zundler","orcid":null,"position":78,"is_corresponding":false},{"id":1131,"name":"Rinse K. Weersma","orcid":"0000-0001-7928-7371","position":79,"is_corresponding":false},{"id":5746,"name":"Zlatko Trajanoski","orcid":"0000-0002-0636-7351","position":80,"is_corresponding":false},{"id":1419671,"name":"Erwin F. Wagner","orcid":null,"position":81,"is_corresponding":false},{"id":677839,"name":"Herbert Tilg","orcid":"0000-0002-4235-2579","position":82,"is_corresponding":false},{"id":880642,"name":"Timon E. Adolph","orcid":"0000-0002-4736-830X","position":83,"is_corresponding":false},{"id":1419184,"name":"Almina Jukic","orcid":"0000-0001-8201-1376","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41295942","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}