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A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils

Author

Listed:
  • Zhongwei Xu

    (Karolinska Institute)

  • Bingze Xu

    (Karolinska Institute)

  • Susanna L. Lundström

    (Karolinska Institute)

  • Àlex Moreno-Giró

    (Karolinska Institute
    Redoxis AB)

  • Danxia Zhao

    (Karolinska Institute)

  • Myriam Martin

    (Lund University)

  • Erik Lönnblom

    (Karolinska Institute)

  • Qixing Li

    (Southern Medical University)

  • Alexander Krämer

    (Karolinska Institute)

  • Changrong Ge

    (Karolinska Institute)

  • Lei Cheng

    (Karolinska Institute)

  • Bibo Liang

    (Karolinska Institute
    Southern Medical University)

  • Dongmei Tong

    (Karolinska Institute)

  • Roma Stawikowska

    (Florida Atlantic University)

  • Anna M. Blom

    (Lund University)

  • Gregg B. Fields

    (Florida Atlantic University)

  • Roman A. Zubarev

    (Karolinska Institute)

  • Rikard Holmdahl

    (Karolinska Institute)

Abstract

Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1β secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41561-7
    DOI: 10.1038/s41467-023-41561-7
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    References listed on IDEAS

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