The characteristics of collagen-induced rheumatoid arthritis in macaques and the changes of heart
Lei Zhang1,2,3,4, Haifeng Jiang1,2,3, Zhen Xu1,2,3
1School of Pharmacy and Science, Anhui Medical University, Hefei, Anhui, China.
Background:
Based on human Rheumatoid Arthritis (RA) criteria, this study established a macaque collagen-induced arthritis (CIA) model and a standardized non-human primate (NHP) standardized diagnostic framework. Integrating these tools, we characterized three disease stages (IIR, e-RA, a-RA) and key early biomarkers, thereby providing a robust platform for investigating RA pathogenesis research and conducting preclinical evaluation of humanized macromolecular drugs.
Methods:
CIA was induced in macaques via through immunization with bovine type II collagen emulsified in complete Freund's adjuvant. Disease progression was monitored using multimodal imaging (MRI, CT, X-ray, and ultrasonography), enabling comprehensive assessment of joint edema, vascularity, bone erosion, and cardiopulmonary function.
Results:
The disease progression in CIA macaques was categorized into three stages: IIR (days 14-34), e-RA (days 35-41), and a-RA (days 42-70). Notably, bone erosion progressed independently of the resolution of joint swelling resolution, with a trend toward aggravated severity during the post-swelling phase. Furthermore, cardiac assessments demonstrated that valvular damage primarily affected the tricuspid valve, with more pronounced impairment of right ventricular diastolic function. Additionally, observed pulmonary inflammation suggests potential lung involvement, though its progression throughout the disease course requires further investigation.
Conclusions:
The progression of CIA in macaques can be divided into three stages: IIR (14-34 days), e-RA (35-41 days), and a-RA (42-70 days). For RA patients, bone erosion should be prioritized in clinical monitoring, and cardiac assessment should focus on the tricuspid valve and right ventricular diastolic function.
