The Collagen Antibody Induced Arthritis (CAIA) model is a relevant model for studying the efferent phase of RA, where leukocytes are attracted and respond to the immune complex in the joint. It is induced using a cocktail of antibodies to anti-CII and contains pathogenic features similar to that of RA such as pannus formation, cellular infiltration, synovitis and cartilage/bone destruction.
Benefits of the CAIA model
Figure: Balb/c were administered 2 mg of ArthritoMab antibody cocktail on day 0 followed by a LPS boost on day 3.Unlike competitor products, disease progression is steady and controlled for easy evaluation of prophylactic and therapeutic regimes.
Comparison
ArthritoMab™ | Competitor | |
Epitopes Recognized | CB11, CB10, CB8 | CB11 only |
Disease Progression | Steady & Controlled | Rapid & Severe |
Paw involvement | Consistent & Predominantely rear | Variable & unpredictable |
Animals/vial | 25 | 20 |
Abreviations:
Epitope specificity
The classic CIA model is mediated by autoantibodies which bind to typeII collagen and complement. In mice as well as human RA patients, theantibody response that best correlates with disease is directed againstthe C1, J1 and U1 epitopes. The ArthritoMab™ arthritogenic cocktail of 4 monoclonal antibodies binds to these well-defined epitopes C11b, J1, D3 and U1, which are spread over the entire CII (CB8, CB10 and CB11 fragments). This possibly encourages better immune complex formation on the cartilage surface for the initiation of arthritis and produces consistent and predictable disease in all 4 paws (with predominance for the rear). Competitor products only recognize CB11, which produces variable disease that can contribute to unpredictable involvement in the paws (sometimes more front paw involvment and other times more rear involvement).
Susceptibility
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Hamamura, K., Nishimura, A., Chen, A., Takigawa, S., Sudo, A., & Yokota, H. (2015). Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis.Cellular signalling,27(4), 828-835
Asnagli, H., Martire, D., Belmonte, N., Quentin, J., Bastian, H., Boucard-Jourdin, M., ... & Marchetti, I. (2014). Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis.Arthritis research & therapy,16(3), R115
Ohtsubo-Yoshioka, M., Nunomura, S., Kataoka, T. R., Okayama, Y., & Ra, C. (2013). Fc receptor beta chain deficiency exacerbates murine arthritis in the anti-type II collagen antibody-induced experimental model.Modern rheumatology,23(4), 804-810
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Jacques, P., Lambrecht, S., Verheugen, E., Pauwels, E., Kollias, G., Armaka, M., ... & Elewaut, D. (2013). Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells.Annals of the rheumatic diseases, annrheumdis-2013
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References/Citations: | How the ArthritoMab™ Antibody Cocktail was used: |
The TNF family member APRIL dampens collagen-induced arthritis. Fernandez,L et al.(2012)Ann Rheum Dis doi:10.1136/annrheumdis-2012-202382 | Arthritis was induced in APRIL-Tg DBA/1 mice using 1.5 mg ArthritoMab per mouse. On day 9, 50 ug LPS was administered. Clinical scores were monitored through day 26. |
Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis. Min S. et al. Biochemical and biophysical research communications. 2010; 391(1):1080-6. | Induce arthritis in 8- and 10-week old BALB/c mice.On day 0, mice were injected intraperitoneally with 4 mg of ArthritoMab.On day 3, mice were boosted intraperitoneally with 50 ug of lipopolysacharide in 200 ul sterile PBS. |
Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. McCann FE, et al. Arthritis Res Ther. 2010 Jun; 12(3):R107. | Induced arthritis experiments using six-week-old male BALB/c mice. |
Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis. Soo-Hong Min et al., Biochemical and Biophysical Research Communications 391 (2010) 1080-1086. | Induce arthritis in Female BALB/c mice between 8 and 10 weeks of age.Each mouse received a 4mg intraperitoneal injection on day 0 and a 50ug boost of LPS on day 3. |
The novel small molecule drug Rabeximod is effective in reducing disease severity of mouse models of autoimmune disorders M Hultqvist, K S Nandakumar, U Björklund, and R HolmdahlAnn Rheum Dis, Jan 2009; 68: 130 - 135. | Induce arthritis in BALB/c mice.On day 0, 100 mg/kg (2 mg/mouse) ofArithritoMab was injected to induce arthritis.At day 5 or 3 respectively, lipopolysacharide (LPS) was injected intraperitoneally (50 ug/mouse) to enhance the incidence. |
Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis. Sofia E. Magnusson, Gunnar Pejler, Sandra Kleinau, and Magnus ÅbrinkFASEB J, Mar 2009; 23: 875 - 882. | Induce arthritis in genetically modified mice backcrossed to the arthritis-susceptible DBA/1 strain.Each mouse recieved a total of 4mg of ArthritoMab transferred intravenously in two consecutive days.On the fourth day, a 50ug boost of LPS was given by intraperitoneal injection. |
Dominant-Negative Inhibitors of Soluble TNF Attenuate Experimental Arthritis without Suppressing Innate Immunity to Infection Jonathan Zalevsky et al.,J. Immunol., Aug 2007; 179: 1872 - 1883. | Induce arthritis in Male BALB/c mice.Each mouse recieved 25 mg/kg of ArthitoMab through i.v. injection on day 0 and a 2.5 mg/kg boost of LPS given by i.p. 72 h later. |
PRECLINICAL EFFICACY OF XPROTM 1595, A BIOLOGIC DOMINANT-NEGATIVE INHIBITOR OF SOLUBLE TNF THAT BLOCKS INFLAMMATION WITHOUT SUPPRESSING INNATE IMMUNITY J. Zalevsky, P. Wong, C. O"Brien, and D.E. SzymkowskiAnn Rheum Dis, Jun 2006; 65: 142. |
Applications
For more information on the ArthritoMab™ Antibody cocktail, download a detailed protocol guide and data pack.
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