Suppression of autoreactive T and B lymphocytes by anti-annexin A1 antibody in a humanized NSG murine model of systemic lupus erythematosus.
N MihaylovaP ChipinskiS BradyanovaT VelikovaE Ivanova-TodorovaS ChaushevaM HerbáthD KalinovaJ PrechlD KyurkchievAndrey Ivanov TchorbanovPublished in: Clinical and experimental immunology (2019)
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.
Keyphrases
- systemic lupus erythematosus
- disease activity
- end stage renal disease
- cell proliferation
- newly diagnosed
- chronic kidney disease
- ejection fraction
- rheumatoid arthritis
- mouse model
- peritoneal dialysis
- type diabetes
- poor prognosis
- endothelial cells
- single cell
- monoclonal antibody
- bariatric surgery
- depressive symptoms
- cell death
- physical activity
- cell cycle
- binding protein
- weight loss
- human health
- obese patients
- cell free