MRZ Reaction: Helps to distinguish MS from its mimics
Background Some rheumatologic disorders (RD) may initially manifest with central nervous system (CNS) affection, mimicking the clinical, magnetic resonance imaging, and cerebrospinal fluid (CSF) findings of multiple sclerosis (MS). Vice versa MS might be difficult to separate from some RD because of the presence of autoantibodies (e.g. ANA) in up to 50%. The MRZ reaction (MRZR), composed of the three respective antibody indices (AI) against measles, rubella, and varicella zoster virus, has been found positive frequently in MS patients. However, it is unclear whether the MRZR is helpful to distinguish rheumatologic disorders with CNS involvement (RDwCNS) from MS.
Objectives To investigate the MRZ reaction as a diagnostic tool to distinguish patients with RDwCNS from patients with MS.
Methods The MRZR was evaluated in 35 patients with RDwCNS and compared to 70 sex- and age- matched MS patients. An AI result ≥1.5 was indicative for intrathecal IgG production against the respective pathogen. Two previously established stringency levels, MRZR-1 (≥1 of 3 AIs positive) and MRZR-2 (≥2 of 3 AIs positive), were applied. CNS involvement of RDwCNS was defined as clinical manifestation with neurological symptoms and signs of inflammation in CSF analysis and/or cerebral/spinal magnetic resonance imaging (MRI). MRZR results were compared using the Fisher’s exact test with p<0.05 for statistical significance.
Results Within the RDwCNS group, 31 patients suffered from systemic lupus erythematosus, four had a small vessel vasculitis. In both groups 77.1% were female, mean age (±SD) was 43.2 years (±18.7) in RDwCNS and 47.5 years (±7.8) in MS (p=n .s.). All RDwCNS patients showed clinical symptoms indicative for CNS involvement and signs of inflammation in CSF analyses and/or MRI of the brain. In 52 MS patients autoantibody screening was performed. 42% were positive for ANA (n=20) or ANCA (n=2) in indirect immunofluorescence. Only 14.3% of RDwCNS patients had a positive MRZR-1 compared to 85.7% within the MS group (p<0.0001). The more specific MRZR-2 was positive in 60% of the MS patients compared to only 8.5% of the RDwCNS patients (p<0.0001). By using a higher threshold of >2.0 for a positive AI, the prevalence of positive MRZR-2 dropped to 5.7% (n=2) in the RDwCNS group compared to 54.3% (n=38) in the MS group (p<0.0001). Oligoclonal bands were found in 94.3% of the MS and 28.6% of the RDwCNS patients (p<0.0001).
Conclusions Considering the high specificity of the MRZR-2 for MS confirmed in this study, this laboratory test may be a helpful diagnostic tool to distinguish RDwCNS from MS.