A astrocyte marker a target for autoimmunity in MS

de Bock L, Somers K, Fraussen J, Hendriks JJ, van Horssen J, Rouwette M, Hellings N, Villar LM, Alvarez-Cermeño JC, Espiño M, Hupperts R, Jongen P, Damoiseaux J, Verbeek MM, De Deyn PP, D’hooghe M, Van Wijmeersch B, Stinissen P, Somers V. Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis. J Immunol. 2014 Aug 1. pii: 1401166. [Epub ahead of print]

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.

SPAG16 encodes 2 major proteins one that associates with the sperm tail and the other is found in a number of places. This study suggests that it is in astrocytes. When you get antibodies against it, it is disease causing because they causes problems when injected in the mice. As is usual we will have to see if this is repeatable, but yet another non-myelin target. 

Is it the chicken or the egg, whereby damage to astrocytes can lead to antibodies that target astrocytes being formed rather than the primary cause.

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1 comment

  • MD,

    you mention the chicken and egg problem – should these studies not be using other neurological diseases and healthy people as controls?

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