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Suppression of autoreactive T and B lymphocytes by anti‐annexin A1 antibody in a humanized NSG murine model of systemic lupus erythematosus.
- Source :
- Clinical & Experimental Immunology; Mar2020, Vol. 199 Issue 3, p278-293, 16p, 2 Diagrams, 1 Chart, 5 Graphs
- Publication Year :
- 2020
-
Abstract
- Summary: Systemic lupus erythematosus is a chronic inflammatory disease which involves multiple organs. Self‐specific B and T cells play a main role in the pathogenesis of lupus and have been defined as a logical target for selective therapy. The protein annexin A1 (ANX A1) is a modulator of the immune system involving many cell types. An abnormal expression of ANX A1 was found on activated B and T cells during autoimmunity, suggesting its importance as a potential therapeutic target. We hypothesize that it may be possible to down‐regulate the activity of autoreactive T and B cells from lupus patients in a humanized immunodeficient mouse model by treating them with an antibody against ANX A1. When cultured in the presence of anti‐ANX A1, peripheral blood mononuclear cells (PBMC) from lupus patients showed a decreased number of immunoglobulin (Ig)G anti‐dsDNA antibody‐secreting plasma cells, decreased T cell proliferation and expression of activation markers and increased B and T cell apoptosis. We employed a humanized model of SLE by transferring PBMCs from lupus patients to immunodeficient non‐obese diabetic‐severe combined immunodeficient (NOD‐SCID) mice. The humanized animals presented autoantibodies, proteinuria and immunoglobulin deposition in the renal glomeruli. Treatment of these NOD‐SCID mice with an anti‐ANX A1 antibody prevented appearance of anti‐DNA antibodies and proteinuria, while the phosphate‐buffered saline (PBS)‐injected animals had high levels after the transfer. The treatment reduced the levels of autoantibodies to several autoantigens, lupus‐associated cytokines and disease symptoms. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 199
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 141660280
- Full Text :
- https://doi.org/10.1111/cei.13399