Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition
- Amara, Khaled Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Steen, Johanna Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Murray, Fiona Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Morbach, Henner Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
- Fernandez-Rodriguez, Blanca M. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Joshua, Vijay Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Engström, Marianne Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Snir, Omri Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Israelsson, Lena Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Catrina, Anca I. Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Wardemann, Hedda Max Planck Research Group Molecular Immunology, Max Planck Institute for Infection Biology, D-10117 Berlin, Germany
- Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Meffre, Eric Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
- Klareskog, Lars Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
- Malmström, Vivianne Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Solna, Stockholm, Sweden
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25.02.2013
Published in:
- The journal of experimental medicine. - 2013, vol. 210, no. 3, p. 445-455
English
Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class II–driven T cell help, remain unclarified. To address these questions, we have used a single B cell–based cloning technology to isolate and express immunoglobulin (Ig) genes from joint-derived B cells of active RA patients. We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA+ RA patients, whereas such antibodies were not found in ACPA− patients. The citrulline-reactive monoclonal antibodies did not react with the unmodified arginine peptides, yet several reacted with more than one citrullinated antigen. A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA+ antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences.
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 324426
- DOI 10.1084/jem.20121486
- ARK ark:/12658/srd1318861
- Persistent URL
- https://n2t.net/ark:/12658/srd1318861
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