Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis

• Published in: The Journal of immunology (1950) Vol. 193; no. 5; pp. 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, Álvarez-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: Journal Article
• Language: English
• Published: United States 01.09.2014
• 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; 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.