title: Annexin A2, autoimmunity, anxiety and depression.
abstract: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model.
  
  
  
  Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11.
  
  
  
  Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% ± 0.89% of the time in the center compared to 8.64% ± 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes.
  
  
  
  We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain.
authors.affiliation: Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Weiss
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Bitton
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Ben Shimon
authors.affiliation: BBB-Group, The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Elhaik Goldman
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Nahary
authors.affiliation: BBB-Group, The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Israel; The Interdisciplinary Center, Herzliya, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Cooper
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Benhar
authors.affiliation: Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Department of Anatomy, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: C G
authors.initials: CG
authors.lastname: Pick
authors.affiliation: Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel; Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: joab.chapman@sheba.health.gov.il.
authors.forename: J
authors.initials: J
authors.lastname: Chapman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D017306:Annexin A2 / Q000276:immunology* / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000523:psychology*; D001007:Anxiety / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D001921:Brain / Q000473:pathology; D003863:Depression / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D055503:Protein Multimerization; D011581:Psychological Tests; D011994:Recombinant Proteins / Q000276:immunology; D009418:S100 Proteins / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D000276:Adjuvants, Immunologic; D000305:Adrenal Cortex Hormones; D017306:Annexin A2; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human
keywords: Annexin; Antiphospholipid syndrome; Anxiety; Autoimmunity; Depression; P11; S100A10