gms | German Medical Science

46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

19.09. - 22.09.2018, Mannheim

The MRZ reaction and specific autoantibody formation assist in the distinction between ANA-positive multiple sclerosis and rheumatic diseases with cerebral involvement

Meeting Abstract

  • Nils Venhoff - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Jens Thiel - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Ana C. Venhoff - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Sebastian Rauer - Klinik für Neurologie und Neurophysiologie, Universitätsklinikum Freiburg, Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Daniela Huzly - Institut für Virologie, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Theresa Schleyer - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Carolin Hentze - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Reinhard Voll - Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
  • Marta Rizzi - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Tilman Hottenrott - Klinik für Neurologie und Neurophysiologie, Universitätsklinikum Freiburg, Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg
  • Ulrich Salzer - Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg; Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Mannheim, 19.-22.09.2018. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocVK.12

doi: 10.3205/18dgrh193, urn:nbn:de:0183-18dgrh1932

Published: February 5, 2019

© 2019 Venhoff et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background: 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. A positive MRZ-reaction (MRZR), which is composed of three antibody indices (AI) against measles, rubella, and varicella zoster virus, determined in paired samples from serum and cerebrospinal fluid (CSF) is frequently positive in MS. Goal of this study was to investigate, whether MRZR and testing for extractable nuclear antigens (ENA) is useful to distinguish RDwCNS from ANA-positive MS.

Methods: MRZR was evaluated in 40 patients with RDwCNS and compared to 68 ANA-positive MS patients. An AI result ≥1.5 was indicative for intrathecal IgG-production against the respective pathogen. Two stringency levels, MRZR-1 and MRZR-2 (≥1/3 AIs respectively ≥2/3 positive) were applied. Autoantibody diagnostics included ANA, ENA (+DFS70), antiphospholipid-antibodies (APA), and antineutrophil cytoplasmic antibodies (ANCA). 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).

Results: Within the RDwCNS-group, 32 patients (80%) suffered from systemic lupus erythematosus, eight had a small vessel vasculitis. In both groups >70% were female. There was no statistical difference between the two groups regarding age and sex. All MS patients were ANA-positive in indirect immunofluorescence. ENA and APA were found more frequently in RDwCNS (p<0.0001). No presence of DFS70-antibodies was detected in the RDwCNS-group, but in 2.9% of the MS-patients. Only 20% of RDwCNS-patients had a positive MRZR-1 compared to 80.9% 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 for a positive AI (>2.0), the prevalence of positive MRZR-2 dropped to 2.5% (n=1) in RDwCNS compared to 36.8% (n=25) in MS-patients (p<0.0001). Oligoclonal bands were found in 89.7% of the MS and 32.6% of the RDwCNS-patients (p<0.0001). In absence of specific autoantibodies a positive MRZR separates RDwCNS from MS with a specificity of 97.5%.

Conclusion: Considering the high specificity we suggest combining MRZR and autoantibody diagnostics to differentiate RDwCNS from MS.