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

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


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Autoantibodies
  • Biomarkers
  • Microtubule-Associated Proteins
  • SPAG16 protein, human