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. 2009 Nov 5;4(11):e7638.
doi: 10.1371/journal.pone.0007638.

IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome

Johannes Brettschneider  1 , Hayrettin Tumani, Ulrike Kiechle, Rainer Muche, Gayle Richards, Vera Lehmensiek, Albert C Ludolph, Markus Otto
Affiliations

IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome

Johannes Brettschneider et al. PLoS One. .

Abstract

Background: Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI.

Methodology/principal findings: MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%).

Conclusions/significance: Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy.

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Conflict of interest statement

Competing Interests: GR is a paid employee of Genzyme Virotech. She contributed to the manuscript by performing the ELISA assays blinded to all other data. She was not involved in study design, data analysis or the decision to publish this manuscript. All other authors have no competing interests to disclose. The authors hereby declare that this does not alter the adherence of all authors to the PLoS One policies on sharing data and materials.

Figures

Figure 1
Figure 1. MRZR in patients with CIS.
Figure shows biomarkers that help to evaluate the risk of multiple sclerosis in patients with clinically isolated syndrome (CIS). MRI  =  lesion load in T2-weighted magnetic resonance imaging (lesions >3 mm2), OCB  =  oligoclonal bands in cerebrospinal fluid (CSF), MRZR  =  MRZ reaction, antibodies to measles, rubella and varicella zoster virus in CSF with two or more AI (antibody indices) ≥1.5. RRMS  =  relapsing-remitting multiple sclerosis.
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