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A subset of type-II...
A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils
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- Xu, Zhongwei (author)
- Karolinska Institutet,Karolinska Institute
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- Xu, Bingze (author)
- Karolinska Institute
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- Lundström, Susanna L. (author)
- Karolinska Institutet,Karolinska Institute
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- Moreno-Giró, Àlex (author)
- Karolinska Institute
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- Zhao, Danxia (author)
- Karolinska Institute
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- Martin, Myriam (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Lönnblom, Erik (author)
- Karolinska Institute
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- Li, Qixing (author)
- Southern Medical University
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- Krämer, Alexander (author)
- Karolinska Institute
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- Ge, Changrong (author)
- Karolinska Institute
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- Cheng, Lei (author)
- Karolinska Institute
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- Liang, Bibo (author)
- Karolinska Institute,Southern Medical University
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- Tong, Dongmei (author)
- Karolinska Institute
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Stawikowska, Roma (author)
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Protein Chemistry, Malmö,Lund University Research Groups
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Fields, Gregg B. (author)
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- Zubarev, Roman A. (author)
- Karolinska Institutet,Karolinska Institute
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- Holmdahl, Rikard (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Communications. - 2041-1723. ; 14:1
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Xu, Zhongwei
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Xu, Bingze
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Lundström, Susan ...
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Moreno-Giró, Àle ...
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Zhao, Danxia
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Martin, Myriam
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show more...
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Lönnblom, Erik
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Li, Qixing
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Krämer, Alexande ...
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Ge, Changrong
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Cheng, Lei
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Liang, Bibo
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Tong, Dongmei
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Stawikowska, Rom ...
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Blom, Anna M.
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Fields, Gregg B.
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Zubarev, Roman A ...
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Holmdahl, Rikard
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Karolinska Institutet