title: Adverse effects of a SOD1-peptide immunotherapy on SOD1 G93A mouse slow model of amyotrophic lateral sclerosis.
abstract: Previous reports from our lab had shown that some anti-purinergic receptor P2X4 antibodies cross-reacted with misfolded forms of mutant Cu/Zn superoxide dismutase 1 (SOD1), linked to amyotrophic lateral sclerosis (ALS). Cross-reactivity could be caused by the abnormal exposure of an epitope located in the inner hydrophobic region of SOD1 that shared structural homology with the P2X4-immunizing peptide. We had previously raised antibodies against human SOD1 epitope mimicked by the P2X4 immunizing peptide. One of these antibodies, called AJ10, was able to recognize mutant/misfolded forms of ALS-linked mutant SOD1. Here, we used the AJ10 antigen as a vaccine to target neurotoxic species of mutant SOD1 in a slow mouse model of ALS. However, the obtained results showed no improvement in life span, disease onset or weight loss in treated animals; we observed an increased microglial neuroinflammatory response and high amounts of misfolded SOD1 accumulated within spinal cord neurons after AJ10 immunization. An increase of immunoglobulin G deposits was also found due to the treatment. Finally, a significantly worse clinical evolution was displayed by an impairment on motor function as a consequence of AJ10 peptide immunization.
authors.affiliation: Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sábado
authors.affiliation: Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Casanovas
authors.affiliation: Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Rodrigo
authors.affiliation: Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Arqué
authors.affiliation: Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain. Electronic address: josep.esquerda@mex.udl.cat.
authors.forename: J E
authors.initials: JE
authors.lastname: Esquerda
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007167:Immunotherapy / Q000009:adverse effects*; D007249:Inflammation / Q000139:chemically induced*; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000009:adverse effects* / Q000276:immunology; D058848:Receptors, Purinergic P2X4 / Q000737:chemistry / Q000276:immunology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000009:adverse effects / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D000072105:Superoxide Dismutase-1
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D008840:Microfilament Proteins; D010455:Peptides; D058848:Receptors, Purinergic P2X4; C000606290:SOD1 protein, human; C109415:SOD1 G93A protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: amyotrophic lateral sclerosis; conformational-specific antibody; immunotherapy; microglia; neuroinflammation; superoxide dismutase