Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by dysfunction of immune regulation, overproduction of inflammatory cytokines and attack on normal tissues by self-reactive cells and antibodies. The main role in the pathogenesis plays the autoreactive tandem of B-T cells, responsible for lupus progression and acceleration. Both activated B and T cells express a phospholipid binding protein Annexin A1 and abnormal levels of the protein were found in murine and human autoimmune syndromes, potentiating its role as a therapeutic target. Here, using anti-annexin A1 antibody we explore its property to modulate the autoimmune response in MRL/lpr mouse model of lupus. Anti-ANX A1 antibody was tested in vitro using spleen cells from MRL/lpr mice to determine the effect on lymphocyte activation, plasma cells differentiation, apoptosis and proliferation by flow cytometry and ELISpot assays. Subsequently, several groups of young (disease-free) and old (sick) MRL/lpr mice were treated with the antibody to determine the levels of panel auto-antibodies and cytokines, T cell arrest and migration. Treatment of splenocytes with anti-ANX A1 antibody inhibited T-cell activation and proliferation, suppressed anti-dsDNA antibody-producing plasma cells and affected B cell apoptosis. Administration of the antibody to MRL/lpr mice resulted to decreased autoantibody levels to various lupus antigens, suppressed T cell migration from lymph nodes and increased the levels of IL4 mRNA compared to the control group. Anti-ANX A1 antibody therapy suppresses B and T cell over-activation and down- modulates disease activity.
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Systemic lupus erythematosus
- ELISpot assay:
Enzyme linked immunospot assay
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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). 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 discussion and ideas.
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Bradyanova, S., Mihaylova, N., Chipinski, P. et al. Anti-ANX A1 Antibody Therapy in MRL/lpr Murine Model of Systemic Lupus Erythematosus. Arch. Immunol. Ther. Exp. 69, 19 (2021). https://doi.org/10.1007/s00005-021-00624-7
- Systemic lupus
- Anti-annexin A1 antibody
- MRL/Lpr mice
- Antibody therapy