Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells

Fan, Kexing, Dai, Jianxin, Wang, Hao, Wei, Huafeng, Cao, Zhiguo, Hou, Sheng, Qian, Weizhu, Wang, Huaqing, Li, Bohua, Zhao, Jian, Xu, Huji, Yang, Chengde and Guo, Yajun (2008) Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells. Arthritis and Rheumatism, 58 7: 2041-2052. doi:10.1002/art.23490


Author Fan, Kexing
Dai, Jianxin
Wang, Hao
Wei, Huafeng
Cao, Zhiguo
Hou, Sheng
Qian, Weizhu
Wang, Huaqing
Li, Bohua
Zhao, Jian
Xu, Huji
Yang, Chengde
Guo, Yajun
Title Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1002/art.23490
Volume 58
Issue 7
Start page 2041
End page 2052
Total pages 12
Place of publication Hoboken, NJ United States
Publisher John Wiley and Sons Inc
Collection year 2008
Language eng
Formatted abstract
Objective
To test the effects of a novel monoclonal antibody (mAb) against human osteopontin (OPN) in the prevention and treatment of collagen-induced arthritis (CIA) and to elucidate the underlying mechanisms of these effects.

Methods
DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of anti-OPN mAb on the clinical severity of the disease, and pathologic changes in the joints were examined histologically. The effects of anti-OPN mAb on survival of activated T cells from arthritic mice and from the synovial fluid of patients with rheumatoid arthritis (RA) were determined by TUNEL assay or annexin V assay. The levels of apoptosis-related proteins (Bim, Bax, and Bcl-2) and NF-κB were detected by immunoblot analysis.

Results
One anti-OPN mAb, 23C3, was effective in inhibiting the development of CIA and even reversing established disease in DBA/1J mice. Monoclonal antibody 23C3 reduced the levels of serum type II collagen–specific autoantibodies and proinflammatory cytokines, and suppressed T cell recall responses to type II collagen. Mechanistic studies demonstrated that OPN prevented the death of type II collagen–activated murine T cells and synovial T cells from RA patients. Monoclonal antibody 23C3 promoted apoptosis of the activated T cells, particularly CD4+ T cells, by inhibiting activation of NF-κB and by altering the balance among the proapoptotic proteins Bim and Bax and the antiapoptotic protein Bcl-2. Screening of a phage display peptide library led to identification of the epitope ATWLNPDPSQKQ as being recognized by this novel antibody.

Conclusion
Because of its ability to effectively promote apoptosis of activated T cells, mAb 23C3 may be a novel therapeutic agent for the treatment of RA. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes ERA

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 11 Sep 2014, 19:17:19 EST by Debra McMurtrie on behalf of Queensland Brain Institute