- Overview
- Data/Specifications
- Literature/Support
- How To Use
- Related Products
Overview
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
- Length of study: Arthritis develops in mice typically within 24-48 hr allowing the completion of a study within 2 weeks reducing the number of assessments and scoring periods.
- Reduced group size: Rate of incidence is nearly 100% depending on the strain allowing for smaller group sizes.
- Synchronization: onset of disease is synchronized between animals simplifying treatment schedules.
- Steady & Controlled disease progression: No rapid & severe disease spikes enabling evaluation of all treatment schedules
- Susceptibility: Arthritis is induced not only in CIA-susceptible DBA/1 and B10.RIII mice, but also in some CIA-resistant mice, such as Balb/c.
- Eliminates expensive colonies: Models such as the K/BxN serum transfer model require labs to maintain expensive colonies and the sera can vary from batch to batch.
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:
- Anti-Collagen Induced arthritis (ACIA)
- Monoclonal Antibody induced arthritis (mAb-RA)
- Collagen Antibody Induced Arthritis (CAIA)
Data/Specifications
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
- Balb/c
- DBA/1
- B10.RIII
- C57Bl/6
Literature/Support
- ArthritoMab™ Antibody Cocktail Product Insert
- Whitepaper: For induction of arthritis in the Collagen Antibody Induced Arthritis (CAIA)model: a shorter, more synchronized alternative to the classic CIA model or K/BxN model.
- Poster: ArthritoMab™ Antibody Cocktail: a cocktail of anti-collagen type II antibodies induce a synchronized model of Arthritis in just 12 days.
- Publication: Efficient promotion of collagen antibody induced arthritis (CAIA)using four monoclonal antibodies specific for the majorepitopes recognized in both collagen induced arthritisand rheumatoid arthritis. Nandukamar & Holmdahl Journal of Immunological Methods 304 (2005) 126 – 136
Nandakumar, K. S., Collin, M., Happonen, K. E., Lundström, S. L., Croxford, A. M., Xu, B., ... & Holmdahl, R. (2018). Streptococcal endo--N-acetylglucosaminidase suppresses antibody mediated inflammation in vivo.Frontiers in immunology,9, 1623.
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
Leavenworth, J. W., Tang, X., Kim, H. J., Wang, X., & Cantor, H. (2013). Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells.The Journal of clinical investigation,123(3), 1382-1389.
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
Kudryavtseva, E., Forde, T. S., Pucker, A. D., & Adarichev, V. A. (2012). Wnt signaling genes of murine chromosome 15 are involved in sex‐affected pathways of inflammatory arthritis.Arthritis & Rheumatism,64(4), 1057-1068
Te Boekhorst, B. C., Jensen, L. B., Colombo, S., Varkouhi, A. K., Schiffelers, R. M., Lammers, T., ... & Nicolay, K. (2012). MRI-assessed therapeutic effects of locally administered PLGA nanoparticles loaded with anti-inflammatory siRNA in a murine arthritis model.Journal of controlled release,161(3), 772-780.
Dimitrova, P., Ivanovska, N., Belenska, L., Milanova, V., Schwaeble, W., & Stover, C. (2012). Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis.Arthritis research & therapy,14(4), R173.
Wruck, C. J., Fragoulis, A., Gurzynski, A., Brandenburg, L. O., Kan, Y. W., Chan, K., ...& Pufe, T. (2010). Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice.Annals of the rheumatic diseases, annrheumdis132720.
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. |
How To Use
Applications
- In vivo: induce disease in the collagen antibody induced arthritis model
- bind collagen in vivo
- impair cartilage formation by chondrocytes in vitro
- inhibit assembly of CII in vitro
- inhibit collagen fibrillogenesis in vitro
- Administer antibody cocktail (IV) on day 0 with 2 mg*
- Boost with LPS on day 3 (IP)
- Body weights, clinical signs & scoring, rear paw thickness
- Terminate on day 12
- Histopathology
For more information on the ArthritoMab™ Antibody cocktail, download a detailed protocol guide and data pack.
