ParadigMS 9th Belgian Symposium 2024

Prof. Romain MARIGNIER – MD, PhD

Pr. Romain Marignier is a neurologist (MD), professor in the Neurological Hospital of Lyon, France. His field of expertise are the neuro-inflammatory disorders of the central nervous system with a specific interest on rare disorders, namely neuromyelitis optica spectrum disorders (NMOSD) and MOG-Ab associated diseases (MOGAD). Pr Marignier is the coordinator of the French nationwide NMO and MOGAD cohorts and biobanks, NOMADMUS, set up in 2010 that includes all the French clinical experts in neuro-inflammatory disorders. Through NOMADMUS, Pr Marignier provided breakthrough insights in the topic regarding clinical characterization, management, and treatment of NMOSD and MOGAD, supported by major publication in high-profile journals.

Since 2017, Pr Marignier is the head of the French referral center for rare inflammatory disorder of the central nervous system (MIRCEM), providing expertise on diagnosis and management of NMOSD and MOGAD for both patients and clinicians.

Finally, Pr. Marignier achieved a PhD on basic neurosciences in 2011 at Claude Bernard University Lyon 1 on the role of auto-antibodies in NMOSD and related diseases. He actually performs his research at INSERM unit 1028 in Lyon Neuroscience Research Centre (CRNL) on: 1. The pathophysiology of auto antibody- mediated disorders of the central nervous system with in vitro, ex vivo and animal models; 2. The development of new strategies to optimise detection of auto-antibodies (anti-AQP4, anti-MOG, anti-GFAP) for diagnosis and prognosis purpose (immunohistochemistry, flow cytometry).

Abstract of talk

In the past 20 years, the concept of antibody mediated demyelinating disorders have emerged. These diseases, namely Aquaporin-4 (AQP4) positive neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte (MOG)- antibody associated disease (MOGAD), share common features with multiple sclerosis, but are fundamentally different in terms of pathophysiology, disease course and treatment. In this lecture we will provide a clinical, biological and imaging description of these two entities, and propose a focus on the features that helps to differentiate in between these conditions.

Learning objectives:

• to know the diagnostic criteria for NMOSD and MOGAD as compared to MS

• to identify the situation when to search for AQP4-IgG and/or MOG-IgG

• to know the principles of attack and preventive therapies of NMOSD and MOGAD

Dr. Laurence LUTTERI

Dr. Laurence Lutteri has a master in pharmacy and a specialization in laboratory medicine. 

She heads the auto-immunity and specialized biochemistry laboratories in the department of clinical chemistry at the University Hospital of Liège.

She collaborates in different projects about connective tissue diseases with rheumatologists, with neurologists for the diagnosis of multiple sclerosis and other inflammatory diseases and also with hematologists for the diagnosis and the follow-up of monoclonal gammopathies.

Immunofluorescence, Elisa, immunodots,…are the different methods used in her auto-immunity laboratory and electrophoresis, immunofixation, turbidimetry, nephelometry and a lot of different manual techniques in the biochemistry laboratory.

Abstract of talk

Various techniques are used in clinical biology laboratories to diagnose inflammatory diseases of the central nervous system (CNS). Detection of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) has been used for many years to diagnose multiple sclerosis. More recently, determination of kappa free light chains in CSF/serum has been developed and offers some advantages : fast, reliable, rater-independent, quantitative results – over OCB technique.

In the differential diagnosis of demyelinating disorders of the CNS, the laboratory’s first-line tests are antibodies targeting aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies on transfected cells (fixed Cell Based Assays (CBA)). In the event of clinically inconsistent results, flow cytometric analysis (live CBA) would show better performance.

Dr. Matthijs OYAERT

Dr. Matthijs Oyaert graduated as a master in drug development (pharmacy) in 2011 and master in  clinical biology in 2016 at the KU Leuven and started working as a clinical biologist at the clinical laboratory of the Ghent University hospital. In the laboratory of clinical chemistry and hematology, he is responsible for a broad variety of (automated) routine clinical chemistry and immunochemistry tests and urinary test strip and particle analysis. In addition, he is involved in the laboratory diagnosis of auto-immune and neuroinflammatory diseases.

During the first years, he obtained his PhD in 2021 entitled “New developments in the laboratory diagnosis of urinary tract pathology” at the Ghent University. Besides his activity in the Sciensano expert group of TDM, chemistry and immunochemistry and member of the European Federation of Laboratory Medicine (EFLM), he is an active Member of the current Royal Belgian Society of Laboratory Medicine (RBSLM) board.

Since 2021, he is involved in the EFLM Task and Finish Group on Urinalysis under the supervision of Prof. Dr. Timo Kouri.

Abstract of talk

Over the last decade, knowledge of antibodies linked to inflammatory disorders of the central nervous system, including forms of neuromyelitis optica (NMO) spectrum disorders, acute disseminated encephalomyelitis (ADEM), optic neuritis and transverse myelitis, has significantly reshaped the landscape of the diagnosis and clinical care. Notably, highly specific antibody assays have become an integral part of clinical decision making and include antibodies directed against the aquaporin-4 and anti–myelin oligodendrocyte glycoprotein (MOG).

Various assays have been developed to identify and quantify anti-MOG. First generation assays, including enzyme-linked immunosorbent assays (ELISA) and western blots, are characterized by a poor sensitivity and specificity. To tackle this disadvantage, during the past 10 years, cell-based assays (CBA) in which the recombinant antigen is expressed in its natural confirmation have been developed. Immunofluorescence or flow cytometry is subsequently employed to visualize and quantify antibody binding. Both live and fixed cell CBAs are utilized, offering enhanced sensitivity and specificity. Moreover, techniques such as immunoprecipitation provide complementary means for MOG antibody detection, allowing for confirmation and characterization of MOG antibody subtypes. The selection of an appropriate assay depends on the diagnostic performance, as well as the laboratory’s technical capabilities.

During this presentation, the different assays for the detection of anti-NMO and anti-MOG antibodies will be discussed, including their performance in the different patient populations. Although a lot of progress has already been made in the development, further efforts need to be undertaken to standardize the different assays.

This valuable learning experience is made possible through the generous support of our sponsors, whom we sincerely thank. It’s important to note that while our sponsors contribute to the success of the event, they have no involvement or influence on the learning content itself. We remain committed to providing an unbiased and enriching educational experience for all participants.

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