IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36257-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36257-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-36257-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhongwei Xu & Bingze Xu & Susanna L. Lundström & Àlex Moreno-Giró & Danxia Zhao & Myriam Martin & Erik Lönnblom & Qixing Li & Alexander Krämer & Changrong Ge & Lei Cheng & Bibo Liang & Dongmei Tong & , 2023. "A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36257-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.