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Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta

Till Andlauer, Jenny Link, Dorothea Martin, Malin Ryner, Christina Hermanrud, Verena Grummel, Michael Auer, Harald Hegen, Lilian Aly, Christiane Gasperi, Benjamin Knier, Bertram Müller-Myhsok, Poul Erik Hyldgaard Jensen, Finn Sellebjerg, Ingrid Kockum, Tomas Olsson, Marc Pallardy, Sebastian Spindeldreher, Florian Deisenhammer, Anna Fogdell-Hahn, Bernhard Hemmer, ,

Background: Upon treatment with biopharmaceuticals, the immune system may produce anti-drug antibodies (ADA) that inhibit the therapy. Up to 40% of multiple sclerosis patients treated with interferon β (IFNβ) develop ADA, for which a genetic predisposition exists. Here, we present a genome-wide association study on ADA and predict the occurrence ... Read more >>

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Late-onset neutropenia in a multiple sclerosis patient after first dose ocrelizumab switched from rituximab.

Michael Auer, Gabriel Bsteh, Harald Hegen, Sebastian Wurth, Anne Zinganell, Thomas Berger, Florian Deisenhammer, Franziska Di Pauli,

Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Before approval of this drug, the chimeric anti-CD20 antibody rituximab was used off-label for treatment of MS. On treatment with rituximab late-onset neutropenia (LON) was reported as a rare adverse event. Here ... Read more >>

Mult Scler Relat Disord (Multiple sclerosis and related disorders)
[2020, 43:102155]

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Influence of physical activity on serum vitamin D levels in people with multiple sclerosis

Angelika Bauer, Ivan Lechner, Michael Auer, Thomas Berger, Gabriel Bsteh, Franziska Di Pauli, Harald Hegen, Sebastian Wurth, Anne Zinganell, Florian Deisenhammer,

Abstract Background : In most cases, multiple sclerosis (MS) patients reduce physical activity with disease progression and many patients are found to be vitamin D deficient. The aim of this study was to evaluate the effect of daily physical activity in everyday life on 25-hydroxyvitamin-D 3 (25(OH)D 3 ) serum ... Read more >>

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International multicenter examination of MOG antibody assays.

Markus Reindl, Kathrin Schanda, Mark Woodhall, Fiona Tea, Sudarshini Ramanathan, Jessica Sagen, James P Fryer, John Mills, Bianca Teegen, Swantje Mindorf, Nora Ritter, Ulrike Krummrei, Winfried Stöcker, Juliane Eggert, Eoin P Flanagan, Melanie Ramberger, Harald Hegen, Kevin Rostasy, Thomas Berger, Maria Isabel Leite, Jacqueline Palace, Sarosh R Irani, Russell C Dale, Christian Probst, Monika Probst, Fabienne Brilot, Sean J Pittock, Patrick Waters,

OBJECTIVE:To compare the reproducibility of 11 antibody assays for immunoglobulin (Ig) G and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG and MOG-IgM) from 5 international centers. METHODS:The following samples were analyzed: MOG-IgG clearly positive sera (n = 39), MOG-IgG low positive sera (n = 39), borderline negative sera (n = 13), ... Read more >>

Neurol Neuroimmunol Neuroinflamm (Neurology(R) neuroimmunology & neuroinflammation)
[2020, 7(2):]

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Commentary to "Letter to the editor: To treat or not to treat study - Comparative group inclusion considerations" for multiple sclerosis and related disorders.

Gabriel Bsteh, Harald Hegen, Thomas Berger,

Mult Scler Relat Disord (Multiple sclerosis and related disorders)
[2020, 40:101975]

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To treat or not to treat: Sequential individualized treatment evaluation in relapsing multiple sclerosis.

Gabriel Bsteh, Harald Hegen, Carolin Dosser, Michael Auer, Klaus Berek, Sebastian Wurth, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger,

BACKGROUND:The frequency and long-term prognosis of relapsing multiple sclerosis (RMS) never receiving disease-modifying treatment (DMT) is unclear. METHODS:We included 1186 RMS patients with a mean of 17.4 years follow-up and divided them into patients treated with any DMT (DMT) and patients untreated by shared (USD) or patient-autonomous decision (UAD). RESULTS:The ... Read more >>

Mult Scler Relat Disord (Multiple sclerosis and related disorders)
[2019, 39:101908]

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An international multicenter examination of MOG antibody assays

Markus Reindl, Kathrin Schanda, Mark Woodhall, Fiona Tea, Sudarshini Ramanathan, Jessica Sagen, Jim Fryer, John Mills, Bianca Tegen, Swantje Mindorf, Nora Ritter, Ulrike Krummrei, Winfried Stocker, Juliane Eggert, Eoin Flanagan, Melanie Ramberger, Harald Hegen, Kevin Rostasy, Thomas Berger, Isabel Leite, Jacqueline Palace, Sarosh Irani, Russell Dale, Christian Probst, Monika Probst, Fabienne Brilot, Sean Pittock, Patrick Waters,

Objectives: To compare the reproducibility of 11 antibody assays for IgG and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG, MOG-IgM) from five international centers. Methods: The following samples were analyzed: MOG-IgG clearly positive sera (n=39), MOG-IgG low positive sera (n=39), borderline negative sera (n=13), clearly negative sera (n=40), and healthy ... Read more >>

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Serum neurofilament light levels correlate with change of olfactory function in multiple sclerosis.

Gabriel Bsteh, Klaus Berek, Harald Hegen, Arabella Buchmann, Margarete M Voortman, Michael Auer, Sebastian Wurth, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Micheal Khalil, Thomas Berger,

Background:Serum neurofilament light chain levels (sNfL) and impairment of olfactory function emerge as biomarkers in multiple sclerosis (MS). However, the relation between sNfL and olfactory function in MS has not been investigated yet. Objective:We aimed to determine whether sNfL levels correlate with olfactory function in relapsing-remitting (RR) MS. Methods:We annually ... Read more >>

Mult Scler J Exp Transl Clin (Multiple sclerosis journal - experimental, translational and clinical)
[2019, 5(4):2055217319885987]

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Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis.

Gabriel Bsteh, Klaus Berek, Harald Hegen, Barbara Teuchner, Arabella Buchmann, Margarete M Voortman, Michael Auer, Sebastian Wurth, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Michael Khalil, Thomas Berger,

BACKGROUND:Serum neurofilament light chain (sNfL) levels and peripapillary retinal nerve fiber layer (pRNFL) are both emerging biomarkers of neuro-axonal damage in multiple sclerosis (MS). However, data on the relation between sNfL and pRNFL are scarce. OBJECTIVE:We aimed to determine the relation of sNfL levels with pRNFL thinning in a large ... Read more >>

Mult. Scler. (Multiple sclerosis (Houndmills, Basingstoke, England))
[2019, :1352458519882279]

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Serum hepcidin levels in multiple sclerosis.

Gabriel Bsteh, David Haschka, Piotr Tymoszuk, Klaus Berek, Verena Petzer, Harald Hegen, Sebastian Wurth, Michael Auer, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Guenter Weiss, Thomas Berger,

Background:Brain iron accumulation is associated with multiple sclerosis (MS). Hepcidin is the master regulator of iron homeostasis and distribution. Dysregulation of hepcidin is a feature of different chronic inflammatory diseases but has not been investigated in MS so far. Objective:The aim of this study was to determine serum hepcidin levels ... Read more >>

Mult Scler J Exp Transl Clin (Multiple sclerosis journal - experimental, translational and clinical)
[2019, 5(4):2055217319885984]

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Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis.

Harald Hegen, Janette Walde, Dejan Milosavljevic, Fahmy Aboulenein-Djamshidian, Makbule Senel, Hayrettin Tumani, Florian Deisenhammer, Stefan Presslauer,

Background Free light chains (FLC) have been proposed as diagnostic biomarkers in the cerebrospinal fluid (CSF) of patients with inflammatory central nervous system (CNS) diseases. However, which method to use for determining an intrathecal FLC synthesis has not yet been clarified. The objective of this study was to compare the ... Read more >>

Clin. Chem. Lab. Med. (Clinical chemistry and laboratory medicine)
[2019, 57(10):1574-1586]

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Conversion and reversion of anti-John Cunningham virus antibody serostatus: A prospective study.

Michael Auer, Harald Hegen, Johann Sellner, Katrin Oppermann, Gabriel Bsteh, Franziska Di Pauli, Thomas Berger, Florian Deisenhammer,

INTRODUCTION:Determination of antibodies against the John Cunningham virus (JCV) is an important tool for risk stratification in Natalizumab-treated multiple sclerosis (MS) patients. Six-monthly testing has been suggested for anti-JCV antibody negative patients and patients with low antibody index in order to detect changes of serostatus. We conducted a prospective study ... Read more >>

Brain Behav (Brain and behavior)
[2019, 9(7):e01332]

Cited: 2 times

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A Survey of Cerebrospinal Fluid Total Protein Upper Limits in Canada: Time for an Update?

Pierre R Bourque, Christopher R McCudden, Jodi Warman-Chardon, John Brooks, Harald Hegen, Florian Deisenhammer, Ari Breiner,

BACKGROUND:The antiquated standard reference range of 0.15-0.45 g/L for cerebrospinal fluid total protein (CSF-TP) is well entrenched in medical literature and laboratory operating procedures across the world. METHODS:We conducted a web-based survey with a response rate of 34.9% through the listserv of the Canadian Neurological Sciences Federation. Additional laboratory reference ... Read more >>

Can J Neurol Sci (The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques)
[2019, 46(3):283-286]

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Dataset for worldwide survey of cerebrospinal total protein upper reference values.

Pierre R Bourque, John Brooks, Jodi Warman-Chardon, Harald Hegen, Florian Deisenhammer, Chris R McCudden, Ari Breiner,

This article reports data pertaining to a worldwide web-based survey referenced in the publication "Adult CSF Total Protein: Higher upper reference limits should be considered worldwide " (P.R. Bourque, et al., 2019). This survey was distributed to corresponding authors of the journal Neurology and the Journal of neurological sciences for ... Read more >>

Data Brief (Data in brief)
[2019, 23:103760]

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The clinical significance of single or double bands in cerebrospinal fluid isoelectric focusing. A retrospective study and systematic review.

Harald Hegen, Anne Zinganell, Michael Auer, Florian Deisenhammer,

BACKGROUND:The presence of ≥3 oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) without corresponding bands in serum represents a definite pathological pattern, whereas the clinical significance of 1-2 CSF bands (borderline pattern) is poorly investigated. METHODS:We screened 1986 consecutive CSF and serum samples which were collected over a four-year time ... Read more >>

PLoS ONE (PloS one)
[2019, 14(4):e0215410]

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Impairment of odor discrimination and identification is associated with disability progression and gray matter atrophy of the olfactory system in MS.

Gabriel Bsteh, Ruth Steiger, Noora Tuovinen, Harald Hegen, Klaus Berek, Sebastian Wurth, Michael Auer, Franziska Di Pauli, Elke R Gizewski, Florian Deisenhammer, Thomas Berger, Christoph Scherfler,

BACKGROUND:Impairment of odor discrimination (D), identification (I), and threshold (T) are characteristic features of multiple sclerosis (MS). OBJECTIVE:To identify patterns of gray matter concentration (GMC) associated with different qualities of olfactory function. METHODS:Olfactory function (T and combined DI score) was measured by Sniffin' Sticks-Test over 2 years longitudinally, and T1-weighted ... Read more >>

Mult. Scler. (Multiple sclerosis (Houndmills, Basingstoke, England))
[2020, 26(6):706-715]

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Adult CSF total protein upper reference limits should be age-partitioned and significantly higher than 0.45 g/L: a systematic review.

Ari Breiner, David Moher, John Brooks, Wei Cheng, Harald Hegen, Florian Deisenhammer, Christopher R McCudden, Pierre R Bourque,

BACKGROUND:Cerebrospinal fluid total protein (CSF-TP) is measured in the diagnosis of a range of immune or infectious disorders of the nervous system. Most laboratories and the medical literature use an antiquated, age-independent upper limit of 0.45 g/L. Therefore, we performed a systematic review of reference studies in the medical literature, with ... Read more >>

J. Neurol. (Journal of neurology)
[2019, 266(3):616-624]

Cited: 2 times

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Pregnancy and multiple sclerosis in the DMT era: A cohort study in Western Austria.

Gabriel Bsteh, Laura Algrang, Harald Hegen, Michael Auer, Sebastian Wurth, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger,

BACKGROUND:Multiple sclerosis (MS) predominantly affects women of child-bearing potential. Pregnancy in MS is still a controversial issue lacking standardized treatment recommendations. OBJECTIVE:To examine the reciprocal effects of pregnancy, MS, and disease-modifying treatment (DMT). METHODS:We analyzed 387 pregnancies in 239 women with relapsing remitting multiple sclerosis (RRMS) and ⩾1 pregnancy, establishment ... Read more >>

Mult. Scler. (Multiple sclerosis (Houndmills, Basingstoke, England))
[2020, 26(1):69-78]

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Smelling multiple sclerosis: Different qualities of olfactory function reflect either inflammatory activity or neurodegeneration.

Gabriel Bsteh, Klaus Berek, Harald Hegen, Barbara Teuchner, Michael Auer, Sebastian Wurth, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger,

BACKGROUND:Peripapillary retinal nerve fiber layer (pRNFL) thickness and olfactory function are both emerging biomarkers in multiple sclerosis (MS). Impairment of odor identification and discrimination is an irreversible feature of more advanced MS suggested to be associated with neurodegeneration, while olfactory threshold is a transient feature of early, active MS possibly ... Read more >>

Mult. Scler. (Multiple sclerosis (Houndmills, Basingstoke, England))
[2020, 26(1):57-68]

Cited: 1 time

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Admission diagnoses of patients later diagnosed with autoimmune encephalitis.

Annette Baumgartner, Sebastian Rauer, Tilman Hottenrott, Frank Leypoldt, Friederike Ufer, Harald Hegen, Harald Prüss, Jan Lewerenz, Florian Deisenhammer, Oliver Stich,

BACKGROUND:Since the detection of autoantibodies against neuronal surface antigens, autoimmune encephalitis (AE) has been more frequently diagnosed, especially in patients with symptoms typical of limbic encephalitis, such as seizures, short-term memory deficits, or psychosis. However, the clinical spectrum of AE may be much wider, making correct clinical diagnosis difficult. METHODS:We ... Read more >>

J. Neurol. (Journal of neurology)
[2019, 266(1):124-132]

Cited: 2 times

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Adult CSF total protein: Higher upper reference limits should be considered worldwide. A web-based survey.

Pierre R Bourque, Ari Breiner, David Moher, John Brooks, Harald Hegen, Florian Deisenhammer, Christopher R McCudden,

BACKGROUND:The cerebrospinal fluid total protein level (CSF-TP) is commonly used as a potential marker of infectious or immune disease of the CNS and PNS. Recent laboratory reference studies indicate that the antiquated single upper reference limit of 0.45 g/L commonly used by hospital laboratories and widely quoted in medical literature is ... Read more >>

J. Neurol. Sci. (Journal of the neurological sciences)
[2019, 396:48-51]

Cited: 2 times

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Impact of Disease-Modifying Treatments on the Longitudinal Evolution of Anti-JCV Antibody Index in Multiple Sclerosis.

Harald Hegen, Janette Walde, Gabriel Bsteh, Michael Auer, Sebastian Wurth, Anne Zinganell, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger,

Background: Risk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies. Objective: To investigate the impact of disease-modifying treatments (DMT) on the longitudinal evolution of anti-JCV antibody index. Methods: Patients with multiple sclerosis who had serum sampling at intervals of 6 ± 3 months over ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:2435]

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Utility of Two-Dimensional Difference Gel Electrophoresis in Diagnosis of Multiple Sclerosis.

Michael Auer, Harald Hegen, Dagmar Rudzki, Georg Golderer, Florian Deisenhammer,

Two-dimensional difference gel electrophoresis (2D-DIGE) has been used for identification of possible biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, in different studies inconsistent results have been obtained. We wanted to analyze the diagnostic value of 2D-DIGE in early MS patients by comparing protein patterns between ... Read more >>

Diagnostics (Basel) (Diagnostics (Basel, Switzerland))
[2018, 8(3):]

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Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis.

Harald Hegen, Dejan Milosavljevic, Christine Schnabl, Andrea Manowiecka, Janette Walde, Florian Deisenhammer, Stefan Presslauer,

BACKGROUND:Free light chains (FLC) have been proposed as diagnostic biomarker in patients with inflammatory central nervous system diseases. The objective of this study was to investigate the diagnostic utility of intrathecal κ- and λ-FLC synthesis in patients with neuroborreliosis. METHODS:κ- and λ-FLC were measured by nephelometry under blinded conditions in ... Read more >>

Clin. Chem. Lab. Med. (Clinical chemistry and laboratory medicine)
[2018, 56(8):1383-1391]

Cited: 1 time

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Autoantibodies against neuronal surface proteins in spontaneous subarachnoid and intracerebral haemorrhage.

Harald Hegen, Raimund Helbok, Mario Kofler, Bettina Pfausler, Alois Schiefecker, Erich Schmutzhard, Ronny Beer,

BACKGROUND:Brain autoimmunity has been reported in patients with preceding infection of the central nervous system by herpesviridae. It has been hypothesized that neuronal damage releasing antigens might trigger secondary immune response. The objective of the study was to investigate whether brain damage due to spontaneous subarachnoid haemorrhage (SAH) or intracerebral ... Read more >>

BMC Neurol (BMC neurology)
[2018, 18(1):89]

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