Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis
BackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assay...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237149/full |
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| author | Benjamin Vlad Benjamin Vlad Ina Reichen Ina Reichen Stephan Neidhart Stephan Neidhart Marc Hilty Marc Hilty Dimitra Lekaditi Dimitra Lekaditi Christine Heuer Christine Heuer Amanda Eisele Amanda Eisele Mario Ziegler Mario Ziegler Markus Reindl Andreas Lutterotti Andreas Lutterotti Axel Regeniter Ilijas Jelcic Ilijas Jelcic |
| author_facet | Benjamin Vlad Benjamin Vlad Ina Reichen Ina Reichen Stephan Neidhart Stephan Neidhart Marc Hilty Marc Hilty Dimitra Lekaditi Dimitra Lekaditi Christine Heuer Christine Heuer Amanda Eisele Amanda Eisele Mario Ziegler Mario Ziegler Markus Reindl Andreas Lutterotti Andreas Lutterotti Axel Regeniter Ilijas Jelcic Ilijas Jelcic |
| author_sort | Benjamin Vlad |
| collection | DOAJ |
| description | BackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.MethodsThis is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).ResultsMOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).ConclusionBasic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria. |
| first_indexed | 2024-03-12T02:09:02Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T02:09:02Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-464456ae97c84ccf819344729a4d5f652023-09-06T16:29:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12371491237149Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosisBenjamin Vlad0Benjamin Vlad1Ina Reichen2Ina Reichen3Stephan Neidhart4Stephan Neidhart5Marc Hilty6Marc Hilty7Dimitra Lekaditi8Dimitra Lekaditi9Christine Heuer10Christine Heuer11Amanda Eisele12Amanda Eisele13Mario Ziegler14Mario Ziegler15Markus Reindl16Andreas Lutterotti17Andreas Lutterotti18Axel Regeniter19Ilijas Jelcic20Ilijas Jelcic21Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandClinical Department of Neurology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandInfectious Disease Serology and Immunology, Medica Medizinische Laboratorien Dr. F. Kaeppeli AG, Zurich, SwitzerlandDepartment of Neurology, University Hospital Zurich, Zurich, SwitzerlandNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, SwitzerlandBackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.MethodsThis is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).ResultsMOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).ConclusionBasic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237149/fullMOGADmultiple sclerosiscerebrospinal fluidMRZ reactionoligoclonal bandsCSF/serum albumin ratio |
| spellingShingle | Benjamin Vlad Benjamin Vlad Ina Reichen Ina Reichen Stephan Neidhart Stephan Neidhart Marc Hilty Marc Hilty Dimitra Lekaditi Dimitra Lekaditi Christine Heuer Christine Heuer Amanda Eisele Amanda Eisele Mario Ziegler Mario Ziegler Markus Reindl Andreas Lutterotti Andreas Lutterotti Axel Regeniter Ilijas Jelcic Ilijas Jelcic Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis Frontiers in Immunology MOGAD multiple sclerosis cerebrospinal fluid MRZ reaction oligoclonal bands CSF/serum albumin ratio |
| title | Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis |
| title_full | Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis |
| title_fullStr | Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis |
| title_full_unstemmed | Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis |
| title_short | Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis |
| title_sort | basic csf parameters and mrz reaction help in differentiating mog antibody associated autoimmune disease versus multiple sclerosis |
| topic | MOGAD multiple sclerosis cerebrospinal fluid MRZ reaction oligoclonal bands CSF/serum albumin ratio |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237149/full |
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