Background and Aims

Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secretion, B cell activation, and promoting amplification of inflammatory response. Annexin A1 is expressed by many cell types and binds to phospholipids in a Ca²⁺ dependent manner. Abnormal expression of annexin A1 was found on activated B/T cells in both murine and human autoimmunity suggesting its potential role as a therapeutic target.

The purpose of our study is to prove that it is possible to down-modulate the activity of autoreactive T and B cells by targeting them with monoclonal antibody against Annexin A1 in lupus-prone MRL/lpr mice.

Methods

Groups of lupus-prone MRL/lpr mice were treated with an anti-annexin A1 monoclonal antibody and the disease activity and survival of the animals were monitored. ELISA and ELISpot assays, RT-PCR, cell proliferation assay, flow cytometry, histological and immunofluorescence kidney analyses were used to determine the levels of cytokines, anti-dsDNA antibodies and kidney injuries.

Results

Administration of anti-annexin A1 monoclonal antibody resulted in suppression of IgG anti-dsDNA antibody production and of proteinuria, modulation of cytokine production, improved kidney histology, decreased disease activity and prolonged survival compared to the control group.

Conclusions

The anti-Annexin A1 antibody therapy targets over-activated autoreactive cells. It has a beneficial effect on earlier stage of lupus development and by using such a therapy it is possible to down-regulate the activity of lupus-associated lymphocytes.