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Updated: Feb 13, 2026

Quantitative Measurement of Intrathecally Synthesized Proteins in Mice
Published on: November 29, 2019
The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central
Tilman Hottenrott1, Elisabeth Schorb2, Kristina Fritsch2
1Department of Neurology and Neurophysiology, Faculty of Medicine, Medical Centre-University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany. tilman.hottenrott@uniklinik-freiburg.de.
Insights
The MRZ reaction (MRZR) in cerebrospinal fluid helps differentiate multiple sclerosis (MS) from primary central nervous system lymphoma (PCNSL). A positive MRZR indicates MS with high specificity, aiding in diagnosis.
Area of Science:
- Neuroimmunology
- Neurology
- Oncology
Background:
- Primary central nervous system lymphoma (PCNSL) can mimic multiple sclerosis (MS) in clinical presentation, MRI, and CSF findings.
- The MRZ reaction (MRZR), assessing antibody indices against measles, rubella, and varicella zoster virus in CSF, is a specific marker for MS.
Purpose of the Study:
- To evaluate the utility of a positive MRZ reaction (MRZR) and other routine cerebrospinal fluid (CSF) markers in distinguishing between MS and PCNSL.
- To assess the diagnostic performance of MRZR using different antibody index (AI) thresholds.
Main Methods:
- Retrospective analysis of CSF and brain biopsy data from 68 PCNSL patients.
- MRZR determination in PCNSL patients (n=37), MS patients (n=74), and psychiatric disorder patients (n=78).
- Application of two AI thresholds (≥1.5 and ≥2.0) for MRZR positivity (≥2 positive AIs).
Main Results:
- Using an AI threshold of ≥1.5, MRZR was positive in 58.1% of MS patients versus 8.1% of PCNSL patients, yielding a positive predictive value (PPV) of 89.6%.
- With a stricter AI threshold of ≥2.0, MRZR was positive in 37.8% of MS patients, while PCNSL and psychiatric disorder patients showed 0% positivity (100% PPV).
- Quantitative intrathecal IgG synthesis was observed in 49.3% of MS patients but none of the PCNSL or psychiatric disorder patients.
Conclusions:
- A positive MRZ reaction (MRZR) demonstrates high specificity and PPV for multiple sclerosis (MS), aiding in its differentiation from primary central nervous system lymphoma (PCNSL).
- The MRZ reaction, particularly with a stricter antibody index threshold, is a valuable tool for distinguishing MS from PCNSL.
- Intrathecal IgG synthesis is another reliable CSF marker that can help differentiate MS from PCNSL.
Abstract:
Some patients with primary central nervous system lymphoma (PCNSL) may initially present with similar clinical, magnetic resonance imaging, and routine cerebrospinal fluid (CSF) findings as those observed in multiple sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, appears to be the most specific CSF marker for MS. This study aimed to determine whether a positive MRZR and other routine CSF markers help differentiate between MS and PCNSL. Data regarding brain biopsy, CSF routine tests, cytopathological examination and immunophenotyping of CSF cells were assessed in 68 PCNSL patients. MRZR was determined, as possible, in PCNSL patients (n = 37) and in those with MS (n = 74; age and sex matched to PSCNL patients) and psychiatric disorders (PD; n = 78). Two stringency levels for a positive antibody index (AI) evaluation (AI ≥ 1.5 and 2.0) were applied, and MRZR was considered positive in cases with ≥ 2 positive AIs (MRZR-2). Using the common AI threshold of ≥ 1.5, MS patients exhibited positive MRZR-2 (58.1%) more frequently than PCNSL (8.1%) and PD patients (2.6%; p < 0.0001 for each comparison with the MS group) corresponding to a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 78.0%. On applying the stricter AI threshold of ≥ 2.0, 37.8% of MS patients were MRZR-2 positive; however, all patients with PCNSL and PD were MRZR-2 negative (p < 0.0001 for each comparison with the MS cohort) resulting in a PPV of 100% and an NPV of 71.4%. Consequently, a positive MRZR-2 result may contribute toward the distinction between MS and PCNSL owing to its high specificity and PPV for MS in the context of the present study. Among the other CSF parameters only a quantitative intrathecal IgG synthesis (present in 49.3% of MS patients but in none of the PCNSL or PD patients; p < 0.0001 for each comparison with the MS group) reliably indicated MS rather than PCNSL.
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