The MRZ-Reaction and Specific Autoantibody Detection for Differentiation of ANA-Positive Multiple Sclerosis From Rheumatic Diseases With Cerebral Involvement.

Nils Venhoff,Julian Staniek,Ana Venhoff,Tilman Hottenrott,Carolin Hentze,Dominique Endres,Sebastian Rauer,Daniela Huzly,Marta Rizzi,Reinhard E Voll,Ulrich Salzer,Jens Thiel

doi:10.3389/fimmu.2019.00514

Nils Venhoff, Julian Staniek + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2019.00514

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Abstract

Objective: Rheumatic diseases with involvement of the central nervous system (RDwCNS) may mimic multiple sclerosis (MS). Inversely, up to 60% of MS-patients have antinuclear autoantibodies (ANAs) and may be misdiagnosed as RDwCNS. The detection of antibodies against extractable nuclear antigens (ENA) and oligoclonal bands (OCB) are established valuable diagnostic tools in the differential diagnosis of RDwCNS and MS. The MRZ-reaction (MRZR) is defined by three antibody indices (AIs) against neurotropic viruses and is frequently positive in MS. To investigate the added value of MRZR combined with testing for antibodies against ENAs and OCB detection to distinguish RDwCNS from ANA positive MS.Methods: MRZR was evaluated in RDwCNS (n = 40) and 68 ANA positive MS-patients. Two stringency levels, MRZR-1 and MRZR-2 (at least one respectively two of three AIs positive) were applied. Autoantibody testing included ANA plus ENA and anti-dsDNA antibodies, antiphospholipid antibodies, and anti-neutrophil cytoplasmic antibodies.Results: Most of the RDwCNS patients (n = 32; 80%) suffered from systemic lupus erythematosus. Within the RDwCNS group 20% had a positive MRZR-1 and 8.5% a positive MRZR-2 compared to 80.9 and 60%, respectively within the MS-group (p < 0.0001 for both comparisons). Oligoclonal bands were found in 28.6% of the RDwCNS patients and 94.3% of the MS-patients (p < 0.0001). Conversely, autoantibodies to specific nuclear antigens or phospholipids were found more frequently in RDwCNS. A positive MRZR in conjunction with the absence of ENA autoantibodies distinguished MS from RDwCNS with high specificity (97.5%).Conclusions: We suggest combining MRZR, OCBs, and specific autoantibody diagnostics to differentiate RDwCNS from MS.

Highlights

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS)
Within the RDwCNS group 20% had a positive MRZR-1 and 8.5% a positive MRZR-2 compared to 80.9 and 60%, respectively within the MS-group (p < 0.0001 for both comparisons)
CNS-involvement of RDwCNS was diagnosed based on clinical signs, and the presence of at least one of the following findings: (A) inflammatory cerebrospinal fluid (CSF) (intrathecal immunoglobulin synthesis, increased cellcount, positive CSF specific oligoclonal bands (OCB), or disturbance in the blood-CSF barrier indicated by an increased albumin quotient) or (B) inflammation in brain or spinal magnetic resonance imaging (MRI) compatible with RDwCNS as assessed by board-certified neuroradiologists

Summary

Introduction

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS). Between 20 and 60% of MS-patients have a positive immunofluorescence testing for anti-nuclear antibodies (ANAs) [1, 2] and in rheumatic diseases such as systemic lupus erythematosus (SLE) or anti-neutrophil cytoplasmic-antibodies (ANCA) associated small vessel vasculitides, neuropsychiatric manifestations are common and may mimic magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) findings of MS [3, 4]. As neuropsychiatric symptoms may be the first clinical manifestation of rheumatic diseases with involvement of the central nervous system (RDwCNS) and inflammatory CSF alterations and MS-like lesions in MRI are frequent, the differential diagnosis between RDwCNS and ANA-positive MS is difficult. The detection of oligoclonal bands (OCB), a very sensitive but compared to the MRZR less specific marker for MS, is an indicator for the involvement B-cells in the pathogenesis of MS

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