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Title: | Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis | Authors: | DE BOCK, Laura SOMERS, Klaartje FRAUSSEN, Judith HENDRIKS, Jerome VAN HORSSEN, Jack ROUWETTE, Myrthe HELLINGS, Niels Villar, Luisa M. Alvarez-Cermeno, Jose C. Espino, Mercedes Hupperts, Raymond Jongen, Peter Damoiseaux, Jan Verbeek, Marcel M. De Deyn, Peter P. D'hooghe, Marie VAN WIJMEERSCH, Bart STINISSEN, Piet SOMERS, Veerle |
Issue Date: | 2014 | Publisher: | AMER ASSOC IMMUNOLOGISTS | Source: | JOURNAL OF IMMUNOLOGY, 193 (5), p. 2147-2156 | 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. | Notes: | [de Bock, Laura; Somers, Klaartje; Fraussen, Judith; Hendriks, Jerome J. A.; van Horssen, Jack; Rouwette, Myrthe; Hellings, Niels; Van Wijmeersch, Bart; Stinissen, Piet; Somers, Veerle] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [de Bock, Laura; Somers, Klaartje; Fraussen, Judith; Hendriks, Jerome J. A.; van Horssen, Jack; Rouwette, Myrthe; Hellings, Niels; Van Wijmeersch, Bart; Stinissen, Piet; Somers, Veerle] Transnatl Univ Limburg, B-3590 Diepenbeek, Belgium. [van Horssen, Jack] Vrije Univ Amsterdam, VU Univ Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 HV Amsterdam, Netherlands. [Villar, Luisa M.; Alvarez-Cermeno, Jose C.; Espino, Mercedes] Hosp Ramon & Cajal, Dept Neurol, E-28034 Madrid, Spain. [Villar, Luisa M.; Alvarez-Cermeno, Jose C.; Espino, Mercedes] Hosp Ramon & Cajal, Dept Immunol, E-28034 Madrid, Spain. [Hupperts, Raymond] Maastricht Univ, Sch Mental Hlth & Neurosci, NL-6229 ER Maastricht, Netherlands. [Hupperts, Raymond] Orbis Med Ctr, Dept Neurol, NL-6130 MB Sittard, Netherlands. [Jongen, Peter] MS4 Res Inst, NL-6522 KJ Nijmegen, Netherlands. [Damoiseaux, Jan] Maastricht Univ, Med Ctr, Cent Diagnost Lab, NL-6202 AZ Maastricht, Netherlands. [Verbeek, Marcel M.] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Brain Cognit & Behav, Dept Neurol, NL-6525 GA Nijmegen, Netherlands. [Verbeek, Marcel M.] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Brain Cognit & Behav, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands. [De Deyn, Peter P.] Univ Antwerp, Lab Neurochem & Behav, B-2610 Antwerp, Belgium. [De Deyn, Peter P.] Univ Antwerp, Inst Born Bunge, Dept Biomed Sci, B-2610 Antwerp, Belgium. [De Deyn, Peter P.] Univ Groningen, Univ Med Ctr, Dept Neurol, NL-9700 RB Groningen, Netherlands. [De Deyn, Peter P.] Middelheim Hosp, Dept Neurol, B-2020 Antwerp, Belgium. [D'hooghe, Marie] Natl MS Ctr, Dept Neurol, B-1820 Melsbroek, Belgium. [D'hooghe, Marie] Vrije Univ Brussel, UZ Brussel, Ctr Neurosci, B-1050 Brussels, Belgium. [Van Wijmeersch, Bart] Rehabil & MS Ctr, B-3900 Overpelt, Belgium. | Keywords: | Immunology | Document URI: | http://hdl.handle.net/1942/17208 | ISSN: | 0022-1767 | e-ISSN: | 1550-6606 | DOI: | 10.4049/jimmunol.1401166 | ISI #: | 000341140600017 | Rights: | Copyright © 2014 by The American Association of Immunologists, Inc. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2015 |
Appears in Collections: | Research publications |
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