title: Sperm-associated antigen 16 is a novel target of the humoral autoimmune response in multiple sclerosis.
abstract: We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16-a protein with unknown function in the CNS-and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo.
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Laura
authors.initials: L
authors.lastname: de Bock
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Klaartje
authors.initials: K
authors.lastname: Somers
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Judith
authors.initials: J
authors.lastname: Fraussen
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium; Department of Molecular Cell Biology and Immunology, VU University Medical Center, VU University Amsterdam, 1081 HV Amsterdam, the Netherlands;
authors.forename: Jack
authors.initials: J
authors.lastname: van Horssen
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Myrthe
authors.initials: M
authors.lastname: Rouwette
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Niels
authors.initials: N
authors.lastname: Hellings
authors.affiliation: Department of Neurology, Ramón y Cajal Hospital, 28034 Madrid, Spain; Department of Immunology, Ramón y Cajal Hospital, 28034 Madrid, Spain;
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Department of Neurology, Ramón y Cajal Hospital, 28034 Madrid, Spain; Department of Immunology, Ramón y Cajal Hospital, 28034 Madrid, Spain;
authors.forename: José C
authors.initials: JC
authors.lastname: Alvarez-Cermeño
authors.affiliation: Department of Neurology, Ramón y Cajal Hospital, 28034 Madrid, Spain; Department of Immunology, Ramón y Cajal Hospital, 28034 Madrid, Spain;
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espiño
authors.affiliation: School of Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, the Netherlands; Department of Neurology, Orbis Medical Center, 6130 MB Sittard, the Netherlands;
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: MS4 Research Institute, 6522 KJ Nijmegen, the Netherlands;
authors.forename: Peter
authors.initials: P
authors.lastname: Jongen
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Centre, 6202 AZ Maastricht, the Netherlands;
authors.forename: Jan
authors.initials: J
authors.lastname: Damoiseaux
authors.affiliation: Department of Neurology, Donders Centre for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Laboratory Medicine, Donders Centre for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands;
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.affiliation: Laboratory of Neurochemistry and Behaviour, University of Antwerp, 2610 Antwerp, Belgium; Department of Biomedical Sciences, Institute Born Bunge, University of Antwerp, 2610 Antwerp, Belgium; Department of Neurology, University Medical Center, University of Groningen, 9700 RB Groningen, the Netherlands; Department of Neurology, Middelheim Hospital, 2020 Antwerp, Belgium;
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Department of Neurology, National MS Center, 1820 Melsbroek, Belgium; Center for Neurosciences, UZ Brussel, Vrije Universiteit Brussel, 1050 Brussels, Belgium; and.
authors.forename: Marie
authors.initials: M
authors.lastname: D'hooghe
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium; Rehabilitation and MS Center, 3900 Overpelt, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van Wijmeersch
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
authors.affiliation: Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium; veerle.somers@uhasselt.be.
authors.forename: Veerle
authors.initials: V
authors.lastname: Somers
mesh_terms: D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; C450619:SPAG16 protein, human