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A subset of antibod...
A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis.
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- He, Yibo (author)
- Karolinska Institutet
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Ge, Changrong (author)
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Moreno-Giró, Àlex (author)
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Xu, Bingze (author)
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Beusch, Christian M (author)
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- Sandor, Katalin (author)
- Karolinska Institutet
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Su, Jie (author)
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Cheng, Lei (author)
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- Lönnblom, Erik (author)
- Karolinska Institutet
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- Lundqvist, Christina, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Slot, Linda M (author)
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Tong, Dongmei (author)
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- Urbonaviciute, Vilma (author)
- Karolinska Institutet
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Liang, Bibo (author)
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Li, Taotao (author)
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Lahore, Gonzalo Fernandez (author)
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- Aoun, Mike (author)
- Karolinska Institutet
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- Malmström, Vivianne (author)
- Karolinska Institutet
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Rispens, Theo (author)
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Ernfors, Patrik (author)
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- Svensson, Camilla I (author)
- Karolinska Institutet
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Scherer, Hans Ulrich (author)
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Toes, René E M (author)
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- Gjertsson, Inger, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Ekwall, Olov, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Clinical Sciences, Department of Pediatrics
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- Zubarev, Roman A (author)
- Karolinska Institutet
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2023-02-08
- 2023
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Abstract
Subject headings
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- 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 certainRA 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- 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)
Keyword
- Humans
- Animals
- Mice
- Autoantibodies
- Proteomics
- Arthritis
- Rheumatoid
- Phosphopyruvate Hydratase
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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He, Yibo
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Ge, Changrong
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Moreno-Giró, Àle ...
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Xu, Bingze
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Beusch, Christia ...
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Sandor, Katalin
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show more...
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Su, Jie
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Cheng, Lei
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Lönnblom, Erik
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Lundqvist, Chris ...
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Slot, Linda M
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Tong, Dongmei
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Urbonaviciute, V ...
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Liang, Bibo
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Li, Taotao
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Lahore, Gonzalo ...
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Aoun, Mike
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Malmström, Vivia ...
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Rispens, Theo
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Ernfors, Patrik
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Svensson, Camill ...
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Scherer, Hans Ul ...
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Toes, René E M
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Gjertsson, Inger ...
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Ekwall, Olov, 19 ...
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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 Clinical Medicin ...
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and Rheumatology and ...
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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 ...
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Nature communica ...
- By the university
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University of Gothenburg
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Karolinska Institutet