{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:55:43Z","timestamp":1788306943492,"version":"build-2803163510"},"reference-count":24,"publisher":"Georg Thieme Verlag KG","issue":"CP","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Research Council -Advanced grant 2023"},{"name":"Max Nieuwdorp is supported by a personal ZONMW-VICI grant 2020"},{"name":"Manon Balvers is appointed on a NNF CAMIT grant 2018 to Max Nieuwdorp"},{"name":"Dagmar van Mourik is supported by a personal Dutch Heart Foundation Dekker grant to Thijs van Mens"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies (aPL), mainly targeted against \u03b22 glycoprotein 1 (\u03b22GP1). The autoimmune response to \u03b22GP1 is aimed at several B-cell and T-cell epitopes. Molecular mimicry of these epitopes by gut commensal proteins, so-called mimotopes, causing cross-immunization, might contribute to the formation of aPL.<\/jats:p>\n                  <jats:p>To study the potential role of gut microbiome cross-immunization in APS by examining cross-reactivity of aPL with gut commensal mimotope-containing proteins.<\/jats:p>\n                  <jats:p>Fecal microbial metagenome of APS patients was determined using shotgun sequencing. An in-house developed in silico pipeline was used to identify gut commensal proteins that show sequence homology with known \u03b22GP1 B and T cell epitopes in the metagenomic data. An enzyme-linked immunosorbent assay was used to test the identified microbial proteins for IgG cross-reactivity, with plasma of 21 APS patients and 17 control participants.<\/jats:p>\n                  <jats:p>The in silico pipeline resulted in the identification of six gut commensals with a B cell and T cell \u03b22GP1 epitope homologue. Of these, YjjG family noncanonical pyrimidine nucleotidase, one of the candidate-\u03b22GP1 B cell mimicking proteins, showed significantly increased IgG reactivity in APS patients compared to control participants, as well as higher binding of a specific anti-\u03b22GP1 monoclonal antibody than a negative control.<\/jats:p>\n                  <jats:p>Our study shows reactivity of IgG antibodies to YjjG family noncanonical pyrimidine nucleotidase from Roseburia amylophila in APS patients. Insights into the origins of antibody formation may yield new therapeutic targets for improvement of APS treatment.<\/jats:p>","DOI":"10.1055\/a-2868-5248","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:46:21Z","timestamp":1778885181000},"source":"Crossref","is-referenced-by-count":1,"special_numbering":"S","title":["Cross-Reactivity of Antiphospholipid Antibodies with Gut Commensal Proteins in Antiphospholipid Syndrome"],"prefix":"10.1055","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-8974","authenticated-orcid":false,"given":"Dagmar J.M.","family":"van Mourik","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, South Holland, the Netherlands","place":["Leiden"],"department":["Department of Internal Medicine, Division of Thrombosis and Hemostasis"]},{"name":"Leiden University Medical Center, South Holland, the Netherlands","place":["Leiden"],"department":["Einthoven Laboratory for Vascular and Regenerative Medicine"]},{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, North Holland, the Netherlands","place":["Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Balvers","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie L.B.I.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, North Holland, the Netherlands","place":["Amsterdam"]},{"name":"Amsterdam Reproduction and Development, North Holland, the Netherlands","place":["Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]},{"name":"Amsterdam Gastroenterology, Endocrinology and Metabolism; Endocrinology, Metabolism and Nutrition, Amsterdam UMC, North Holland, the Netherlands","place":["Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Coppens","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, North Holland, the Netherlands","place":["Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Middeldorp","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Gelderland, the Netherlands","place":["Nijmegen"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen C.J.","family":"Eikenboom","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, South Holland, the Netherlands","place":["Leiden"],"department":["Department of Internal Medicine, Division of Thrombosis and Hemostasis"]},{"name":"Leiden University Medical Center, South Holland, the Netherlands","place":["Leiden"],"department":["Einthoven Laboratory for Vascular and Regenerative Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Voorberg","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular Medicine"]},{"name":"Sanquin Research, North Holland, the Netherlands","place":["Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs E.","family":"van Mens","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, South Holland, the Netherlands","place":["Leiden"],"department":["Department of Internal Medicine, Division of Thrombosis and Hemostasis"]},{"name":"Amsterdam UMC, Location University of Amsterdam, North Holland, the Netherlands","place":["Amsterdam"],"department":["Department of Vascular 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