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  • Li, T. T.Karolinska Institute (author)

Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023-03-01
  • BMJ,2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/325729
  • https://gup.ub.gu.se/publication/325729URI
  • https://doi.org/10.1136/ard-2022-223633DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-206885URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-193032URI
  • https://lup.lub.lu.se/record/d0772a80-495f-4a1f-b6c6-c916835af06eURI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152240146URI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Knut and Alice Wallenberg Foundation [KAW 2019.0059]; Swedish Association against Rheumatism [R-757331]; Swedish Research Council [2019-01209, 20210383]; Swedish Association against Rheumatism [2019-01140]; Foundation for Assistance to Disabled People in Skane, Sweden; Heart and Lung foundation [R-931878]; LUA/ALF [ALFGBG-718851]
  • ObjectivesTo identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). MethodsIgG 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. ResultsPeptide GPI(293-307) 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 GPI(293-307) epitopes, and high affinity anti-GPI(293-307) IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI(293-307) IgG antibodies induced arthritis in mice. Moreover, anti-GPI(293-307) IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI(293-307)-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-GPI(293-307) antibodies. ConclusionsWe 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ge, C. R.Karolinska Institute (author)
  • Kramer, A.Karolinska Institutet,Karolinska Institute (author)
  • Sareila, Outi,1976Karolinska Institutet,Karolinska Institute,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Rheumatology and Inflammation Research, University of Gothenburg, Sahlgrenska Academy, Göteborg, Sweden,Karolinska Inst, Sweden; Univ Gothenburg, Sweden(Swepub:gu)xsarou (author)
  • Leu Agelii, Monica,1977Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Department of Rheumatology and Inflammation Research, University of Gothenburg, Sahlgrenska Academy, Göteborg, Sweden,Univ Gothenburg, Sweden(Swepub:gu)xleumo (author)
  • Johansson, LindaUmeå University,Umeå universitet,Reumatologi,Umea Univ, Sweden(Swepub:umu)lijo0115 (author)
  • Forslind, KristinaLund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Spenshults artrit grupp,Forskargrupper vid Lunds universitet,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Rheumatology,Section III,Department of Clinical Sciences, Lund,Spenshults arthritis group,Lund University Research Groups(Swepub:lu)med-kfi (author)
  • Lonnblom, E.Karolinska Institutet,Karolinska Institute (author)
  • Yang, M.Karolinska Institute (author)
  • Xu, B. Z.Karolinska Institute (author)
  • Li, Q. X.Center for Medical Immunopharmacology Research, Southern Medical University, Guangzhou, China,Southern Med Univ, Peoples R China (author)
  • Cheng, L.Karolinska Institute (author)
  • Bergstrom, G.Department of Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden,Sahlgrens Univ Hosp, Sweden (author)
  • Fernandez, G.Karolinska Institute (author)
  • Kastbom, AlfLinköping University,Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)alfka05 (author)
  • Rantapää-Dahlqvist, SolbrittUmeå University,Umeå universitet,Reumatologi,Umea Univ, Sweden(Swepub:umu)sora0001 (author)
  • Gjertsson, Inger,1962Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Department of Rheumatology and Inflammation Research, University of Gothenburg, Sahlgrenska Academy, Göteborg, Sweden; Rheumatology, Sahlgrenska University Hospital, Göteborg, Sweden,Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden(Swepub:gu)xgjein (author)
  • Holmdahl, R.Karolinska Institutet,Karolinska Institute (author)
  • Karolinska InstitutetKarolinska Institute (creator_code:org_t)

Related titles

  • In:Annals of the Rheumatic Diseases: BMJ82:6, s. 799-8080003-49671468-2060

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