Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes

Arthritis Research & Therapy

Shaw-Wei D. Tsen¹  Krishna Sharmah Gautam¹  Amir Kucharski¹  Kexian Liang¹  Rui Tang¹  Gail Sudlow¹  Samuel Achilefu¹  Luke E. Springer²  Christine T. N. Pham² 

[1] Departments of Radiology, Washington University School of Medicine;Division of Rheumatology, Washington University School of Medicine;

关键词: Near-infrared fluorescent imaging;    Treatment response monitoring;    Inflammatory arthritis;    Rheumatoid arthritis;   

DOI  :  10.1186/s13075-021-02643-3

来源: DOAJ

【 摘 要 】

Abstract Background The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response. Methods LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined by histological and immunohistochemical methods. Results In mouse models of spontaneous and serum transfer-induced inflammatory arthritis, intravenously administered LS301 showed selective accumulation in regions of joint pathology including paws, ankles, and knees with positive correlation between fluorescent signal and disease severity by clinical scoring. Whole-body near-infrared imaging with LS301 allowed tracking of spontaneous disease remission and the therapeutic response after dexamethasone treatment. Histological analysis showed preferential accumulation of LS301 within the chondrocytes and articular cartilage in arthritic mice, and colocalization was observed between LS301 and pANXA2 in the joint tissue. Conclusions We demonstrate that fluorescence imaging with LS301 can be used to monitor the progression, remission, and early response to drug treatment in mouse models of RA. Given the ease of detecting LS301 with portable optical imaging devices, the agent may become a useful early treatment response reporter for arthritis diagnosis and drug evaluation.

【 授权许可】

Unknown