Monoclonal antibody therapy that targets phospholipid‐binding protein delays lupus activity in MRL/lpr mice

Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. Together with B cells, respective self‐reactive T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secreti...

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Published in:Scandinavian journal of immunology 2020-09, Vol.92 (3), p.e12915-n/a
Main Authors: Mihaylova, Nikolina, Bradyanova, Silviya, Chipinski, Petroslav, Chausheva, Stela, Kyurkchiev, Dobroslav, Tchorbanov, Andrey I.
Format: Article
Language:English
Subjects:
Antibodies
antibody therapy
Antigens
anti‐annexin A1 antibody
Autoantibodies
Autoimmunity
autoreactive T and B cells
Calcium
Cell activation
Cytokines
Enzyme-linked immunosorbent assay
Flow cytometry
Immunofluorescence
Immunoglobulin G
Immunotherapy
Inflammation
Kidneys
Lupus
Lymphocytes B
Lymphocytes T
Monoclonal antibodies
MRL/lpr mice
Phospholipids
systemic lupus
Systemic lupus erythematosus
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Summary:Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. Together with B cells, respective self‐reactive T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secretion, B cell activation and promoting amplification of the autoimmune 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 and T cells in both murine and human autoimmunity suggesting its potential role as a therapeutic target. In the present study, we have investigated the possibility to suppress autoimmune manifestation in spontaneous mouse model of lupus using anti‐annexin A1 antibody. Groups of lupus‐prone MRL/lpr mice were treated with the anti‐annexin A1 monoclonal antibody, and the disease activity and survival of the animals were following up. Flow cytometry, ELISA assays, and histological and immunofluorescence kidney analyses were used to determine the levels of Annexin A1 expression, cytokines, anti‐dsDNA antibodies and kidney injuries. The administration of this monoclonal antibody to MRL/lpr mice resulted in suppression of IgG anti‐dsDNA antibody production, modulated IL‐10 secretion, decreased disease activity and prolonged survival compared with the control group.
ISSN:0300-9475
1365-3083
DOI:10.1111/sji.12915