Experimental model of antigen-collagen induced arthritis in mice

Abstract

Introduction. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases with a complex pathogenesis. To develop and test new methods and approaches in RA therapy (biological preparations, cell technologies), an experimental model with similar pathogenetic reactions and immunological changes is needed. One such approach is the development of models of combined antigen-collagen-induced arthritis.

The aim of the study is to show the immunological and histological changes similar to RA in the antigen-collagen induced arthritis (AIA/CIA) model and the validity of its application in research activities and for the development of new therapeutic approaches.

Material and methods. Experimental AIA/CIA was induced according to 3 different protocols in 60 Balb/c mice. Arthritis was assessed visually by measuring paw swelling with a caliper at different times. The assessment of immunological changes included the analysis of the content of antibodies to type II collagen by ELISA, the content of T-regulatory cells by flow cytometry. In addition, a histological examination of the tissues of the joints was carried out, followed by an analysis of the data obtained.

Results. On the 10th day, a significant increase in the thickness of the paws was recorded in animals using the induction of experimental arthritis with different protocols. The intensity of swelling subsided by the 23rd day. A significant increase in the content of antibodies to type II collagen was observed in all experimental groups, but in animals on Protocol No. 1, the level of antibodies to type II collagen was significantly higher. A high level of T-regulatory cells was registered only in mice on Protocol No. 1 on the 10th day. Histological changes in the form of synovial hyperplasia, pannus, usurations were observed to varying degrees in all experimental groups, but the most pronounced changes were in animals on Protocol No. 1.

Conclusion. In experimental animals, in all the presented protocols, changes were observed that were closest to RA, when compared with classical models of experimental arthritis induction. Based on the fact that protocol 1 animals showed an increase in the content of T-regulatory cells, the levels of antibodies to type II collagen were consistently high, and histological changes were the most pronounced, it can be assumed that Protocol No. 1 of the combined AIA/CIA model on the Balb/c mice line is the most suitable for testing and developing of new methods for RA therapy.

Keywords:rheumatoid arthritis; arthritis model; experimental arthritis; collagen antigen-induced arthritis

For citation: Fisher M.S., Kurilin V.V., Tereshchenko V.P., Bulygin A.S., Kuznetsova M.S., Ivleva E.K., Sennikov S.V. Experimental model of antigen-collagen-induced arthritis in mice. Immunology. 2022; 43 (2): 157–65. DOI: https://doi.org/10.33029/0206-4952-2022-43-2-157-165 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contributions. The concept and design of the study – Kurilin V.V., Fisher M.S., Sennikov S.V.; collection and processing of material – Fisher M.S., Kurilin V.V., Bulygin A.S., Ivleva E.K.; statistical processing – Fisher M.S., Tereshchenko V.P., Kuznetsova M.S.; text writing – Fisher M.S.; text edition – Sennikov S.V., Tereshchenko V.P.

References

1. Croia C., Bursi R., Sutera D., Petrelli F., Alunno A., Puxeddu I. One year in review 2019: pathogenesis of rheumatoid arthritis. Clin. Exp. Rheumatol. 2019; 37 (3): 347–57. PMID: 31111823.

2. Abbasi M., Mousavi M.J., Jamalzehi S., Alimohammadi R., Bezvan M.H., Mohammadi H., Aslani S. Strategies toward rheumatoid arthritis therapy; the old and the new. J. Cell. Physiol. 2018; 234 (7): 10 018–31. DOI: https://doi.org/10.1002/jcp.27860

3. Greenberg J.D., Reed G., Kremer J.M., Tindall E., Kavanaugh A., Zheng C., Bishai W., Hochberg M.C.; CORRONA Investigators. Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry. Ann. Rheum. Dis. 2010; 69 (2): 380–6. DOI: https://doi.org/10.1136/ard.2008.089276

4. Avdeeva Zh.I., Soldatov A.A., Bondarev V.P., Merkulov V.A., Medunitsyn N.V. The problems concerned with undesirable immunogenicity of biotechnological medicines (therapeutic proteins). Part 1. Methodological approaches to the evaluation of immunogenicity. Immunologiya. 2019; 40 (3): 51–64. DOI: https://doi.org/10.24411/0206-4952-2019-13006 (in Russian)

5. Brand D.D. Rodent models of rheumatoid arthritis. Comp. Med. 2005; 55 (2): 114–22. PMID: 15884771.

6. Choudhary N., Bhatt L.K., Prabhavalkar K.S. Experimental animal models for rheumatoid arthritis. Immunopharmacol. Immunotoxicol. 2018; 40 (3): 193–200. DOI: https://doi.org/10.1080/08923973.2018.1434793

7. Bessis N., Decker P., Assier E., Semerano L., Boissier M.C. Arthritis models: usefulness and interpretation. Semin. Immunopathol. 2017; 39 (4): 469–86. DOI: https://doi.org/10.1007/s00281-017-0622-4

8. Baddack U., Hartmann S., Bang H., Grobe J., Loddenkemper C., Lipp M., Müller G.A chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice. Nat. Commun. 2013; 4 (1): 1–10. DOI: https://doi.org/10.1038/ncomms2625

9. Asquith D.L., Miller A.M., McInnes I.B., Liew F.Y. Animal models of rheumatoid arthritis. Eur. J. Immunol. 2009; 39: 2040–4. DOI: https://doi.org/10.1002/eji.200939578

10. Lindqvist A.K.B., Bockermann R., Johansson Å.C., Nandakumar K.S., Johannesson M., Holmdahl R. Mouse models for rheumatoid arthritis. Trends Genet. 2002; 18 (6): S7–13. DOI: https://doi.org/10.1016/S0168-9525(02)02684-7

11. Komarova E.B. Synovial membrane changes in patients with rheumatoid arthritis revealed during arthroscopy. Nauchno-prakticheskaya revmatologiya. 2017; 55 (3): 241–4. DOI: http://dx.doi.org/10.14412/1995-4484-2017-241-244 (in Russian)

12. López-Longo F.J., Oliver-Miñarro D., de la Torre I., González-Díaz de Rábago E., Sánchez-Ramón S., et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Care Res. 2009; 61 (4): 419–24. DOI: https://doi.org/10.1002/art.24390

13. Cantaert T., Teitsma C., Tak P.P., Baeten D. Presence and role of anti-citrullinated protein antibodies in experimental arthritis models. Arthritis Rheum. 2013; 65 (4): 939–48. DOI: https://doi.org/10.1002/art.37839

14. Kim W.U., Yoo W.H., Park W., Kang Y.M., Kim S.I., Park J.H., Kim H.Y. IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis. J. Rheumatol. 2000; 27 (3): 575–81. PMID: 10743792.

15. Bugatti S., Codullo V., Caporali R., Montecucco C.B cells in rheumatoid arthritis. Autoimmun. Rev. 2007; 7 (2): 137–42. DOI: https://doi.org/10.1016/j.autrev.2007.02.017

16. Vallbracht I., Rieber J., Oppermann M., Förger F., Siebert U., Helmke K. Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Ann. Rheum. Dis. 2004; 63 (9): 1079–84. DOI: http://dx.doi.org/10.1136/ard.2003.019877

17. Cho Y.G., Cho M.L., Min S.Y., Kim H.Y. Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis. Autoimmun. Rev. 2007; 7 (1): 65–70. DOI: https://doi.org/10.1016/j.autrev.2007.08.001

18. van Venrooij W.J., Zendman A.J., Pruijn G.J. Autoantibodies to citrullinated antigens in (early) rheumatoid arthritis. Autoimmun. Rev. 2006; 6 (1): 37–41. DOI: https://doi.org/10.1016/j.autrev.2006.03.008

19. Kim W.U., Cho M.L., Jung Y.O., Min S.Y., Park S.W., Min D.J., Kim H.Y. Type II collagen autoimmunity in rheumatoid arthritis. Am. J. Med. Sci. 2004; 327 (4): 202–11. DOI: https://doi.org/10.1097/00000441-200404000-00006

20. Furuzawa-Carballeda J., Vargas-Rojas M.I., Cabral A.R. Autoimmune inflammation from the Th17 perspective. Autoimmun. Rev. 2007; 6 (3): 169–75. DOI: https://doi.org/10.1016/j.autrev.2006.10.002

21. Lubberts E., Koenders M.I., van den Berg W.B. The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res. Ther. 2004; 7 (1): 1–9. DOI: https://doi.org/10.1186/ar1478

22. Scalapino K.J., Tang Q., Bluestone J.A., Bonyhadi M.L., Daikh D.I. Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J. Immunol. 2006; 177 (3): 1451–9. DOI: https://doi.org/10.4049/jimmunol.177.3.1451

23. Cajas L.J., Casallas A., Medina Y.F., Quintana G., Rondón F. Pannus and rheumatoid arthritis: Historic and pathophysiological evolution. Rev. Colomb. Reumatol. 2019; 26 (2): 118–28. DOI: https://doi.org/10.1016/j.rcreue.2018.10.005

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