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

• Published in: The Journal of immunology (1950) 2014-09, Vol.193 (5), p.2147-2156
• Main Authors: de Bock, Laura, Somers, Klaartje, Fraussen, Judith, Hendriks, Jerome J A, van Horssen, Jack, Rouwette, Myrthe, Hellings, Niels, Villar, Luisa M, Alvarez-Cermeño, José C, Espiño, Mercedes, Hupperts, Raymond, Jongen, Peter, Damoiseaux, Jan, Verbeek, Marcel M, De Deyn, Peter P, D'hooghe, Marie, Van Wijmeersch, Bart, Stinissen, Piet, Somers, Veerle
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibody Specificity; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers - blood; Brain - immunology; Brain - metabolism; Brain - pathology; Encephalomyelitis, Autoimmune, Experimental - blood; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoelectric Focusing; Male; Mice; Microtubule-Associated Proteins - blood; Microtubule-Associated Proteins - immunology; Middle Aged; Multiple Sclerosis - blood; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401166

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.