Search: WFRF:(Leu Monica 1977)
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Pathogenic antibody...
Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage
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- Li, T. T. (author)
- Karolinska Institute
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- Ge, C. R. (author)
- Karolinska Institute
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- Kramer, A. (author)
- Karolinska Institutet,Karolinska Institute
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- Sareila, Outi, 1976 (author)
- Karolinska 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
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- Leu Agelii, Monica, 1977 (author)
- Gothenburg 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
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- Johansson, Linda (author)
- Umeå University,Umeå universitet,Reumatologi,Umea Univ, Sweden
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- Forslind, Kristina (author)
- Lund 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
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- Lonnblom, E. (author)
- Karolinska Institutet,Karolinska Institute
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- Yang, M. (author)
- Karolinska Institute
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- Xu, B. Z. (author)
- Karolinska Institute
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- Li, Q. X. (author)
- Center for Medical Immunopharmacology Research, Southern Medical University, Guangzhou, China,Southern Med Univ, Peoples R China
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- Cheng, L. (author)
- Karolinska Institute
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- Bergstrom, G. (author)
- Department of Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden,Sahlgrens Univ Hosp, Sweden
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- Fernandez, G. (author)
- Karolinska Institute
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- Kastbom, Alf (author)
- Linköping University,Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Rantapää-Dahlqvist, Solbritt (author)
- Umeå University,Umeå universitet,Reumatologi,Umea Univ, Sweden
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- Gjertsson, Inger, 1962 (author)
- Gothenburg 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
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- Holmdahl, R. (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2023-03-01
- 2023
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 799-808
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http://dx.doi.org/10...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- arthritis
- experimental
- rheumatoid
- autoimmunity
- autoantibodies
- inflammation
- cyclic citrullinated peptide
- rheumatoid-arthritis
- synovial-fluid
- anti-glucose-6-phosphate isomerase
- mouse model
- b-cells
- autoantibodies
- autoantigen
- affinity
- serum
- Rheumatology
- arthritis
- arthritis, experimental
- arthritis, rheumatoid
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Li, T. T.
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Ge, C. R.
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Kramer, A.
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Sareila, Outi, 1 ...
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Leu Agelii, Moni ...
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Johansson, Linda
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show more...
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Forslind, Kristi ...
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Lonnblom, E.
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Yang, M.
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Xu, B. Z.
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Li, Q. X.
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Cheng, L.
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Bergstrom, G.
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Fernandez, G.
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Kastbom, Alf
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Rantapää-Dahlqvi ...
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Gjertsson, Inger ...
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Holmdahl, R.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Annals of the Rh ...
- By the university
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University of Gothenburg
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Umeå University
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Linköping University
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Lund University
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Karolinska Institutet