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J Immunol. 2014 Sep 1;193(5):2147-56. doi: 10.4049/jimmunol.1401166. Epub 2014 Aug 1.

Sperm-associated antigen 16 is a novel target of the humoral autoimmune response in multiple sclerosis.

Author information

1
Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium;
2
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;
3
Department of Neurology, Ramón y Cajal Hospital, 28034 Madrid, Spain; Department of Immunology, Ramón y Cajal Hospital, 28034 Madrid, Spain;
4
School of Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, the Netherlands; Department of Neurology, Orbis Medical Center, 6130 MB Sittard, the Netherlands;
5
MS4 Research Institute, 6522 KJ Nijmegen, the Netherlands;
6
Central Diagnostic Laboratory, Maastricht University Medical Centre, 6202 AZ Maastricht, the Netherlands;
7
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;
8
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;
9
Department of Neurology, National MS Center, 1820 Melsbroek, Belgium; Center for Neurosciences, UZ Brussel, Vrije Universiteit Brussel, 1050 Brussels, Belgium; and.
10
Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium; Rehabilitation and MS Center, 3900 Overpelt, Belgium.
11
Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg, 3590 Diepenbeek, Belgium; veerle.somers@uhasselt.be.

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.

PMID:
25086173
DOI:
10.4049/jimmunol.1401166
[Indexed for MEDLINE]
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