{"entity": "publication", "iuid": "143d8fa5b14d4da59b547cdab40f00ee", "timestamp": "2026-08-15T21:32:04.575Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/143d8fa5b14d4da59b547cdab40f00ee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/143d8fa5b14d4da59b547cdab40f00ee"}}, "title": "Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.", "authors": [{"family": "Li", "given": "Taotao", "initials": "T", "orcid": "0000-0001-6775-9976", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f265876c30443b8a8ef616d7029e64a.json"}}, {"family": "Ge", "given": "Changrong", "initials": "C"}, {"family": "Kr\u00e4mer", "given": "Alexander", "initials": "A"}, {"family": "Sareila", "given": "Outi", "initials": "O", "orcid": "0000-0001-5644-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf109dc5ef0c4ad4ac2bd28770555e09.json"}}, {"family": "Leu Agelii", "given": "Monica", "initials": "M", "orcid": "0000-0003-4013-7549", "researcher": {"href": "https://publications.scilifelab.se/researcher/521b91a3f436415e96585996f64b85b1.json"}}, {"family": "Johansson", "given": "Linda", "initials": "L", "orcid": "0000-0001-7071-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9129e8ce7846e5b35b50f1ff4493e2.json"}}, {"family": "Forslind", "given": "Kristina", "initials": "K"}, {"family": "L\u00f6nnblom", "given": "Erik", "initials": "E", "orcid": "0000-0002-1311-2541", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f5683b51d554ff482bd76c0ded3aaa2.json"}}, {"family": "Yang", "given": "Min", "initials": "M"}, {"family": "Xu", "given": "Bingze", "initials": "B", "orcid": "0000-0002-5341-1722", "researcher": {"href": "https://publications.scilifelab.se/researcher/d262ebec52004d1f8bc77d43cafe0cc7.json"}}, {"family": "Li", "given": "Qixing", "initials": "Q"}, {"family": "Cheng", "given": "Lei", "initials": "L"}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Fernandez", "given": "Gonzalo", "initials": "G"}, {"family": "Kastbom", "given": "Alf", "initials": "A", "orcid": "0000-0001-7187-1477", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9b6d835959e4613995904bf3a01733c.json"}}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S", "orcid": "0000-0001-8259-3863", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfca4bfdcf3946fda64397d3b7debc59.json"}}, {"family": "Gjertsson", "given": "Inger", "initials": "I", "orcid": "0000-0002-9301-4844", "researcher": {"href": "https://publications.scilifelab.se/researcher/56e95592e89f43cba8eb30bd32da1cc8.json"}}, {"family": "Holmdahl", "given": "Rikard", "initials": "R", "orcid": "0000-0002-4969-2576", "researcher": {"href": "https://publications.scilifelab.se/researcher/49e60d22dd1a4dd1a4ca5a50d9fc4fc7.json"}}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "volume": "82", "issue": "6", "pages": "799-808", "issn-l": "0003-4967"}, "abstract": "To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA).\n\nIgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining.\n\nPeptide GPI293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI293-307 epitopes, and high affinity anti-GPI293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI293-307-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI293-307 antibodies.\n\nWe have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.", "doi": "10.1136/ard-2022-223633", "pmid": "36858822", "labels": {"Bioinformatics Long-term Support WABI": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "ard-2022-223633"}], "notes": [], "created": "2023-11-23T13:32:53.288Z", "modified": "2023-11-23T13:32:53.448Z"}