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A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis

Author

Listed:
  • Yibo He

    (Karolinska Institutet)

  • Changrong Ge

    (Karolinska Institutet)

  • Àlex Moreno-Giró

    (Karolinska Institutet
    Redoxis AB)

  • Bingze Xu

    (Karolinska Institutet)

  • Christian M. Beusch

    (Karolinska Institutet)

  • Katalin Sandor

    (Karolinska Institutet)

  • Jie Su

    (Karolinska Institutet)

  • Lei Cheng

    (Karolinska Institutet)

  • Erik Lönnblom

    (Karolinska Institutet)

  • Christina Lundqvist

    (University of Göteborg)

  • Linda M. Slot

    (Leiden University Medical Center)

  • Dongmei Tong

    (Karolinska Institutet)

  • Vilma Urbonaviciute

    (Karolinska Institutet)

  • Bibo Liang

    (Karolinska Institutet
    Southern Medical University)

  • Taotao Li

    (Karolinska Institutet)

  • Gonzalo Fernandez Lahore

    (Karolinska Institutet)

  • Mike Aoun

    (Karolinska Institutet)

  • Vivianne Malmström

    (Karolinska Institutet, Karolinska University Hospital)

  • Theo Rispens

    (University of Amsterdam)

  • Patrik Ernfors

    (Karolinska Institutet)

  • Camilla I. Svensson

    (Karolinska Institutet)

  • Hans Ulrich Scherer

    (Leiden University Medical Center)

  • René E. M. Toes

    (Leiden University Medical Center)

  • Inger Gjertsson

    (University of Göteborg)

  • Olov Ekwall

    (University of Göteborg
    University of Göteborg)

  • Roman A. Zubarev

    (Karolinska Institutet)

  • Rikard Holmdahl

    (Karolinska Institutet
    Southern Medical University)

Abstract

Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certain RA synovial fluid proteins such as α-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated α-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA.

Suggested Citation

  • Yibo He & Changrong Ge & Àlex Moreno-Giró & Bingze Xu & Christian M. Beusch & Katalin Sandor & Jie Su & Lei Cheng & Erik Lönnblom & Christina Lundqvist & Linda M. Slot & Dongmei Tong & Vilma Urbonavic, 2023. "A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36257-x
    DOI: 10.1038/s41467-023-36257-x
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    References listed on IDEAS

    as
    1. Takako Negishi-Koga & Hans-Jürgen Gober & Eriko Sumiya & Noriko Komatsu & Kazuo Okamoto & Shinichiro Sawa & Ayako Suematsu & Tomomi Suda & Kojiro Sato & Toshiyuki Takai & Hiroshi Takayanagi, 2015. "Immune complexes regulate bone metabolism through FcRγ signalling," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
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