Annexin A1 as a target for managing murine pristane-induced systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy. Annexin A1 (ANX A1) is expressed by many cell types and binds to phospholipids in a Ca²⁺ dependent manner. Abnormal expression of ANX A1 was found on activated B and T cells in both murine and human autoimmunity, suggesting its potential role as a therapeutic target. While its role on T lymphocytes is through formyl peptide receptor-like molecules (FPRL), and the formed ANX A1/FPRL pathway modulates T cell receptor signalling, there is still no fool-proof data available for the role of ANX A1 in B cells. We employed a lupus model of Balb/c mice with pristane-induced SLE which very closely resembles human lupus. In the present study, we investigated the possibility to modulate the autoimmune response in a pristane-induced mouse model of SLE using an anti- ANX A1 antibody. Administration of this monoclonal antibody resulted in the inhibition of T-cell activation and proliferation, suppression of IgG anti-dsDNA antibody-secreting plasma cells and of proteinuria, decreased disease activity and prolonged survival compared to control group.

Keywords:

• Pristane-induced systemic lupus erythematosus
• Anti-annexin A1 antibody
• Balb/c mice

Acknowledgements

We thank Prof. Fulvio D’Acquisto (William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK) for helpful discussions and ideas. This study was supported by the Bulgarian National Science Fund [grant DDVU 02/34] and Bilateral grant between Bulgarian Academy of Sciences and Hungarian Academy of Sciences [grant contract number SNK-73/2013].

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This study was supported by the Bulgarian National Science Fund [grant DDVU 02/34] and Bilateral grant between Bulgarian Academy of Sciences and Hungarian Academy of Sciences [grant contract number SNK-73/2013].