Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity
<p>Abstract</p> <p>Background</p> <p>The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-11-01
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| Series: | Journal of Inflammation |
| Online Access: | http://www.journal-inflammation.com/content/8/1/31 |
| _version_ | 1818766263281778688 |
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| author | Mizutani Nobuaki Hutamekalin Pilaiwanwadee Kadotani Tatsuya Koobkokkruad Thongchai Yoshino Shin |
| author_facet | Mizutani Nobuaki Hutamekalin Pilaiwanwadee Kadotani Tatsuya Koobkokkruad Thongchai Yoshino Shin |
| author_sort | Mizutani Nobuaki |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII-3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII.</p> <p>Methods</p> <p>DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA.</p> <p>Results</p> <p>First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross-reaction with mouse CII but also marked activation of the complement <it>in vitro</it>.</p> <p>Conclusion</p> <p>The combination of 4 mAbs showing strong abilities to activate the complement and bind mouse CII effectively induced arthritis in DBA/1J mice. This <it>in vitro </it>system may be useful for the selection of mAbs associated with the development of arthritis.</p> |
| first_indexed | 2024-12-18T08:31:12Z |
| format | Article |
| id | doaj.art-76f7273105bf4625b7e2355890489079 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-18T08:31:12Z |
| publishDate | 2011-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-76f7273105bf4625b7e23558904890792022-12-21T21:14:28ZengBMCJournal of Inflammation1476-92552011-11-01813110.1186/1476-9255-8-31Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinityMizutani NobuakiHutamekalin PilaiwanwadeeKadotani TatsuyaKoobkokkruad ThongchaiYoshino Shin<p>Abstract</p> <p>Background</p> <p>The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII-3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII.</p> <p>Methods</p> <p>DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA.</p> <p>Results</p> <p>First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross-reaction with mouse CII but also marked activation of the complement <it>in vitro</it>.</p> <p>Conclusion</p> <p>The combination of 4 mAbs showing strong abilities to activate the complement and bind mouse CII effectively induced arthritis in DBA/1J mice. This <it>in vitro </it>system may be useful for the selection of mAbs associated with the development of arthritis.</p>http://www.journal-inflammation.com/content/8/1/31 |
| spellingShingle | Mizutani Nobuaki Hutamekalin Pilaiwanwadee Kadotani Tatsuya Koobkokkruad Thongchai Yoshino Shin Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity Journal of Inflammation |
| title | Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity |
| title_full | Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity |
| title_fullStr | Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity |
| title_full_unstemmed | Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity |
| title_short | Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity |
| title_sort | arthrogenicity of type ii collagen monoclonal antibodies associated with complement activation and antigen affinity |
| url | http://www.journal-inflammation.com/content/8/1/31 |
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