The establishment of a rheumatoid arthritis primate model in Macaca fascicularis

Hyun Sik Na,Mi-La Cho,Jung-Hwan Lee,Shin-Hee Hong,Dae-Hoon Kim,Ka-Hee Cho,Hong Ki Min,Jooyeon Jhun,Jeong-Won Choi,Seung-Ki Kwok,Seon-Yeong Lee,Wan-Je Park,Sung-Min Kim,Sung-Hwan Park

doi:10.1186/s12967-020-02402-z

Abstract

BackgroundRheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.MethodsWe used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints.ResultsA new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group.ConclusionIn conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.

Highlights

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage
All animal research procedures were conducted in accordance with the Laboratory Animals Welfare Act, the Guide for the Care and Use of Laboratory Animals, and the Guidelines and Policies for Non-human Primate (NHP) Experiments provided by the Institutional Animal Care and Use Committee (ORIENT-IACUC-16255)
The M. fascicularis had the B*01 gene among their major histocompatibility complex (MHC) class I genes, but all were susceptible to collagen-induced arthritis (CIA) induction (Fig. 1)

Summary

Introduction

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies. Rheumatoid arthritis (RA) is an autoimmune-mediated inflammatory disease. Most of the pre-clinical studies are performed on rodent models of RA, such as collagen-induced arthritis (CIA) or antibody-induced arthritis. Na et al J Transl Med (2020) 18:264 a critical failing due to the differences between humans and rodents in terms of morphology, physiology, and phylogenetic closeness [2, 3]. There is an unmet need to establish a better animal model for RA to enhance our knowledge of RA pathogenesis and to conduct pre-clinical experiments using an RA animal model that is similar to humans

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Discussion

Conclusion