title: Annexin A1 as a target for managing murine pristane-induced systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy. Annexin A1 (ANX A1) is expressed by many cell types and binds to phospholipids in a Ca2+dependent manner. Abnormal expression of ANX A1 was found on activated B and T cells in both murine and human autoimmunity, suggesting its potential role as a therapeutic target. While its role on T lymphocytes is through formyl peptide receptor-like molecules (FPRL), and the formed ANX A1/FPRL pathway modulates T cell receptor signalling, there is still no fool-proof data available for the role of ANX A1 in B cells. We employed a lupus model of Balb/c mice with pristane-induced SLE which very closely resembles human lupus. In the present study, we investigated the possibility to modulate the autoimmune response in a pristane-induced mouse model of SLE using an anti- ANX A1 antibody. Administration of this monoclonal antibody resulted in the inhibition of T-cell activation and proliferation, suppression of IgG anti-dsDNA antibody-secreting plasma cells and of proteinuria, decreased disease activity and prolonged survival compared to control group.
authors.affiliation: a Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Mihaylova
authors.affiliation: a Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Silviya
authors.initials: S
authors.lastname: Bradyanova
authors.affiliation: a Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Petroslav
authors.initials: P
authors.lastname: Chipinski
authors.affiliation: b MTA-ELTE Immunology Research Group , Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Melinda
authors.initials: M
authors.lastname: Herbáth
authors.affiliation: a Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Stela
authors.initials: S
authors.lastname: Chausheva
authors.affiliation: c Laboratory of Clinical Immunology, University Hospital 'St.I.Rilski', Medical University Sofia , Sofia , Bulgaria.
authors.forename: Dobroslav
authors.initials: D
authors.lastname: Kyurkchiev
authors.affiliation: b MTA-ELTE Immunology Research Group , Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Prechl
authors.affiliation: a Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Tchorbanov
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D019468:Disease Management; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D058990:Molecular Targeted Therapy; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013729:Terpenes / Q000009:adverse effects*
chemical_list: D017305:Annexin A1; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D013729:Terpenes; C009042:pristane
keywords: Anti-annexin A1 antibody; Balb/c mice; Pristane-induced systemic lupus erythematosus