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  • Sherina, NataliaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (author)

Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells : Implications for a Bacterial Origin in RA Etiology

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-04-20
  • Frontiers Media S.A.2022
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-194875
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-194875URI
  • https://doi.org/10.3389/fimmu.2022.804822DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:149805019URI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

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

Notes

  • Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated P. gingivalis peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from P. gingivalis (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined. B cells from inflamed gingival tissue were single-cell sorted, and immunoglobulin (Ig) genes were amplified, sequenced, cloned and expressed (n=63) as recombinant monoclonal antibodies, and assayed for citrulline-reactivities by enzyme-linked immunosorbent assay. Additionally, affinity-purified polyclonal anti-cyclic-citrullinated peptide (CCP2) IgG, and monoclonal antibodies derived from RA blood and synovial fluid B cells (n=175), were screened for CPP3-reactivity. Elevated anti-CPP3 antibody levels were detected in RA (11%), mainly CCP2+ RA, compared to controls (2%), p<0.0001, with a significant association to HLA-DRB1 shared epitope alleles, smoking and baseline pain, but with low correlation to autoimmune ACPA fine-specificities. Monoclonal antibodies derived from gingival B cells showed cross-reactivity between P. gingivalis CPP3 and human citrullinated peptides, and a CPP3+/CCP2+ clone, derived from an RA blood memory B cell, was identified. Our data support the possibility that immunity to P. gingivalis derived citrullinated antigens, triggered in the inflamed gum mucosa, may contribute to the presence of ACPA in RA patients, through mechanisms of molecular mimicry.

Subject headings and genre

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

  • de Vries, CharlotteKarolinska Institutet (author)
  • Kharlamova, NastyaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (author)
  • Sippl, NatalieDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (author)
  • Jiang, XiaKarolinska Institutet (author)
  • Brynedal, BoelKarolinska Institutet (author)
  • Kindstedt, ElinUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden(Swepub:umu)elki0009 (author)
  • Hansson, MonikaKarolinska Institutet (author)
  • Mathsson-Alm, LindaThermo Fisher Scientific, ImmunoDiagnositic Division, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (author)
  • Israelsson, LenaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (author)
  • Stålesen, RagnhildKarolinska Institutet (author)
  • Saevarsdottir, SaedisKarolinska Institutet (author)
  • Holmdahl, RikardKarolinska Institutet (author)
  • Hensvold, AaseKarolinska Institutet (author)
  • Johannsen, GunnarKarolinska Institutet (author)
  • Eriksson, KajaDivision of Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Orthodontics and Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden (author)
  • Sallusto, FedericaInstitute for Research in Biomedicine, Universita dell a Svizzera Italiana, Bellinzona, Switzerland; Institute of Microbiology, ETH Zurich, Zurich, Switzerland (author)
  • Catrina, Anca I.Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Center for Rheumatology, Academic Specialist Center, Stockholm Health Region, Stockholm, Sweden (author)
  • Rönnelid, JohanDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (author)
  • Grönwall, CarolineKarolinska Institutet (author)
  • Yucel-Lindberg, TülayKarolinska Institutet (author)
  • Alfredsson, LarsKarolinska Institutet (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • Piccoli, LucaInstitute for Research in Biomedicine, Universita dell a Svizzera Italiana, Bellinzona, Switzerland (author)
  • Malmström, VivianneKarolinska Institutet (author)
  • Amara, KhaledDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (author)
  • Lundberg, KarinKarolinska Institutet (author)
  • Karolinska InstitutetDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (creator_code:org_t)

Related titles

  • In:Frontiers in Immunology: Frontiers Media S.A.131664-3224

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