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Cartilage-binding a...
Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthritis
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- Li, Yanpeng (författare)
- Southern Med Univ, SMU KI United Med Inflammat Ctr, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China.,Southern Medical University, Guangzhou, China
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- Tong, Dongmei (författare)
- Karolinska Inst, Dept Med Biochem & Biophys, Med Inflammat Res, SE-17177 Stockholm, Sweden.,Karolinska Institute, Stockholm, Sweden
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- Liang, Peibin (författare)
- Southern Med Univ, SMU KI United Med Inflammat Ctr, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China.,Southern Medical University, Guangzhou, China
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- Lönnblom, Erik (författare)
- Karolinska Institutet,Karolinska Institute, Stockholm, Sweden
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- Viljanen, Johan V. (författare)
- Uppsala universitet,Organisk kemi,Uppsala University, Uppsala, Sweden
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- Xu, Bingze (författare)
- Karolinska Institutet,Karolinska Institute, Stockholm, Sweden
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- Nandakumar, Kutty Selva, 1965- (författare)
- Högskolan i Halmstad,Akademin för företagande, innovation och hållbarhet,Southern Medical University, Guangzhou, China
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- Holmdahl, Rikard (författare)
- Karolinska Institutet,Southern Medical University, Guangzhou, China; Karolinska Institute, Stockholm, Sweden
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Southern Med Univ, SMU KI United Med Inflammat Ctr, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China Southern Medical University, Guangzhou, China (creator_code:org_t)
- 2020-05-24
- 2020
- Engelska.
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Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362. ; 22
- Relaterad länk:
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Antibodies binding to cartilage proteins are present in the blood and synovial fluid of early rheumatoid arthritis patients. In order to develop animal models mimicking the human disease, we have characterized the arthritogenic capacity of monoclonal antibodies directed towards different joint proteins in the cartilage.Methods: Purified antibodies specific to unmodified or citrullinated collagen type II (CII), collagen type XI (CXI), and cartilage oligomeric matrix protein (COMP) were produced as culture supernatant, affinity purified, pooled as antibody cocktails (Cab3 and Cab4), and injected intravenously into mice to induce arthritis. An adjuvant (lipopolysaccharide or mannan) was subsequently injected intraperitoneally on either day 5 or day 60 to enhance arthritis. Antibody binding and complement activation on the cartilage surface were analyzed by immunohistochemical methods. Bone erosions and joint deformations were analyzed by histological assessments, enzyme-linked immunosorbent assays, and micro-CT. Luminex was used to detect CII-triple helical epitope-specific antibody responses.Results: The new cartilage antibody cocktails induced an earlier and more severe disease than anti-CII antibody cocktail. Many of the mouse strains used developed severe arthritis with 3 antibodies, binding to collagen II, collagen XI, and cartilage oligomeric matrix protein (the Cab3 cocktail). Two new models of arthritis including Cab3-induced LPS-enhanced arthritis (lpsCAIA) and Cab3-induced mannan-enhanced arthritis (mCAIA) were established, causing severe bone erosions and bone loss, as well as epitope spreading of the B cell response. Cab4, with addition of an antibody to citrullinated collagen II, induced arthritis more efficiently in moderately susceptible C57BL/6 J mice.Conclusions: The new mouse model for RA induced with cartilage antibodies allows studies of chronic development of arthritis and epitope spreading of the autoimmune response and bone erosion.
Ämnesord
- 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)
Nyckelord
- Rheumatoid arthritis
- Cartilage
- Animal models
- Antibodies
- Collagen
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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