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ArthritoMab™ Antibody Cocktail for inducing Arthritis

Catalog Number: 
50 mg

ArthritoMab antibody cocktail from MD Bioproducts

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data pack and protocol optimization guide for arthritomab antibody cocktailArthritoMab™ Arthritis Inducing Antibody Cocktail is a cocktail of 4 arthritogenic monoclonal antibodies to collagen II (CII) used for inducing arthritis in the anti-Collagen Antibody Induced Arthritis (CAIA) model. It is an excellent alternative to both the K/BxN and CIA models. Induction is rapid and results in a synchronized, steady and controlled disease progression that exhibits histological similarities to the classic CIA model. Download a protocol guide and data pack to learn more about the epitopes, protocol, optimization tips, positive controls and data.



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.

arthritogenic antibody - induce arthritis in the collagen antibody induced arthritis 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.




Epitopes Recognized

CB11, CB10, CB8CB11 only
Disease ProgressionSteady & ControlledRapid & Severe
Paw involvementConsistent & Predominantely rearVariable & unpredictable


  • Anti-Collagen Induced arthritis (ACIA)
  • Monoclonal Antibody induced arthritis (mAb-RA)
  • Collagen Antibody Induced Arthritis (CAIA)



Epitope specificity

The classic CIA model is mediated by autoantibodies which bind to type II collagen and complement. In mice as well as human RA patients, the antibody response that best correlates with disease is directed against the 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).


relevant epitopes in collagen induced arthritis | arthritomab arthritis induced antibody cocktail



  • Balb/c
  • DBA/1
  • B10.RIII
  • C57Bl/6
Disease Progression & Positive controls
Disease progression is steady and controlled using ArthritoMab™ antibody cocktail, enabling investigators to evaluate various regimes. Data below was generated using Vehicle, Dexamethasone and Enbrel in the Balb/c strain (induced with 2 mg ArthritoMab™ on day 0 followed by LPS boost on day 3).
arthritis scores in the collagen antibody induced arthritis using ArthritoMab arthritogenic antibody
Histopathological changes in the joints are scored on a scale of 0-4 for seven different parameters. Histopathology in the balb/c induced with ArthritoMab™ antibody cocktail share similarities with the CIA model.The images below show histological joint changes on day 12 in Balb/c when induced with 2 mg ArthritoMab™ Antibody Cocktail. Synovial Hyperplasia (left), cellular infiltration (middle), cartilage & bone erosion (right).
synovial hyperplasia in Balb/c using 2 mg of ArthritoMab antibody cocktail  cellular infiltration in balb/c using Arthritomab antibody cocktail  bone & cartilage erosion in balb/c using 2 mg Arthritomab antibody cocktail




Sangaletti, S., Botti, L., Gulino, A., Lecis, D., Bassani, B., Portararo, P., ... & Colombo, M. P. (2020). SPARC regulation of PMN clearance protects from pristane induced lupus and rheumatoid arthritis. Available at SSRN 3678911.


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 immunology9, 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 signalling27(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 & therapy16(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 rheumatology23(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 investigation123(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 & Rheumatism64(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 release161(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 & therapy14(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.



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-2012-202382Arthritis 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 Holmdahl Ann Rheum Dis, Jan 2009; 68: 130 - 135.
Induce arthritis in BALB/c mice. On day 0, 100 mg/kg (2 mg/mouse) of ArithritoMab 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 Åbrink FASEB 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.
J. Zalevsky, P. Wong, C. O'Brien, and D.E. Szymkowski Ann Rheum Dis, Jun 2006; 65: 142.





How To Use

How To Use: 


  • 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
For the Induction of Arthritis in the Collagen Antibody Induced Arthritis Model:
  1. Administer antibody cocktail (IV) on day 0 with 2 mg*
  2. Boost with LPS on day 3 (IP)
  3. Body weights, clinical signs & scoring, rear paw thickness
  4. Terminate on day 12
  5. Histopathology
*Needs to be optimized for each laboratory. MD Biosciences contract research service runs the Collagen Antibody Induced Arthritis model using the ArthritoMab™ cocktail on a monthly basis. Scientists can assist in setting up the model in each lab, walking through optimizations not only based on your individual vivarium conditions, but also based on your compound requirements. We use a variety of administration routes and compound classes and can assist in recommending the best approach for your situation.

For more information on the ArthritoMab™ Antibody cocktail, download a detailed protocol guide and data pack.