The intrathecal, polyspecific antiviral immune response: Specific for MS or a general marker of CNS autoimmunity?

Jarius, Sven; Eichhorn, Peter; Jacobi, Christian; Wildemann, Brigitte; Wick, Manfred; Voltz, Raymond

doi:10.1016/j.jns.2008.08.002

« Previous Next »Journal of the Neurological Sciences
Volume 280, Issue 1 , Pages 98-100, 15 May 2009

The intrathecal, polyspecific antiviral immune response: Specific for MS or a general marker of CNS autoimmunity?

Sven Jarius
- Division of Molecular Neuroimmunology, Department of Neurology, Ruprecht Karl University, Heidelberg, Germany
Peter Eichhorn
- Department of Clinical Chemistry, Ludwig Maximilians University, Munich, Germany
Christian Jacobi
- Division of Molecular Neuroimmunology, Department of Neurology, Ruprecht Karl University, Heidelberg, Germany
Brigitte Wildemann
- Division of Molecular Neuroimmunology, Department of Neurology, Ruprecht Karl University, Heidelberg, Germany
Manfred Wick
- Department of Clinical Chemistry, Ludwig Maximilians University, Munich, Germany
Raymond Voltz
- Department of Palliative Medicine, University of Cologne, Cologne, Germany
- Corresponding author. Department of Palliative Medicine, University of Cologne, D-50924 Cologne, Germany. Tel.: +49 221478 3361; fax: +49 221478 87579.

Received 14 March 2008; received in revised form 22 July 2008; accepted 6 August 2008. published online 05 January 2009.

Abstract

Background

80–100% of patients with multiple sclerosis (MS) display a polyspecific, intrathecal humoral immune response against a broad panel of viral agents including antibodies to measles, rubella and varicella zoster virus as its three most abundant components (called MRZ reaction [MRZR]). However, a positive MRZR reaction can also be found in some patients with CNS vasculitis, another rare autoimmune condition, raising the question whether this marker is really of high specificity for MS as previously claimed or whether it just represents a non-specific marker of CNS autoimmunity. Besides MS and CNS vasculitis, paraneoplastic neurological disorders (PND) represent the best recognized models of CNS autoimmunity.

Objective

To investigate MRZR for the first time in patients with PND.

Patients and methods

Forty-two patients with MS and 34 with PND were compared in this study. The intrathecal synthesis of antibodies against measles, rubella, and varicella zoster virus was detected by calculation of the respective antibody indices (AI).

Results

A positive MRZ reaction as defined by a combination of at least two positive AIs was present in 37/42 patients with MS, but in none of the patients with PND (p < 0.0001). Median AI values differed significantly between groups (p < 0.0005).

Conclusions

Our results confirm that MRZR is not a general marker of CNS autoimmunity. Taking into account the very rarity of CNS vasculitis as well the lack of MRZR positivity in infectious inflammatory CNS conditions as previously demonstrated, MRZR might indeed be a promising marker of MS. Further investigations on MRZR in more rare autoimmune conditions, which were not available for analysis in this study, are now warranted to refine further the specificity of this parameter.

Keywords: Multiple sclerosis, Paraneoplastic neurological disorders, CSF marker, Intrathecal IgG synthesis, Measles virus, Rubella virus, Varicella zoster virus