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Anti-ANX A1 Antibody Therapy in MRL/lpr Murine Model of Systemic Lupus Erythematosus

Abstract

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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Abbreviations

SLE:

Systemic lupus erythematosus

ANXA1:

Annexin A1

ConA:

Concanavalin

LPS:

Lipopolysaccharide

ELISpot assay:

Enzyme linked immunospot assay

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Acknowledgements

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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SB investigation and validation, NM investigation, validation, conceptualization, methodology, formal analysis and writing—original draft, PC investigation and validation, YM investigation and validation, Melinda Herbáth investigation and validation, DK conceptualization and methodology, JP conceptualization, methodology and formal analysis, AT conceptualization, methodology, supervision, formal analysis and writing—original draft. All authors read and approved the final manuscript.

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Correspondence to Andrey I. Tchorbanov.

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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

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Keywords

  • Systemic lupus
  • Anti-annexin A1 antibody
  • MRL/Lpr mice
  • Antibody therapy