Molecular biomarkers in multiple sclerosis

Ziemssen, Tjalf; Akgün, Katja; Brück, Wolfgang

doi:10.1186/s12974-019-1674-2

Cited by 182 publications

(171 citation statements)

References 144 publications

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“…MS patients showed an intrathecal production of IgG, IgM, and IgA (Lolli et al, 1989); about 95% of the MS patients displayed IgG OCBs (Link, 1978;Villar et al, 2005), and around 40% also showed intrathecal IgM production (Villar et al, 2005), while CSF IgA synthesis was only occasionally observed (in 13% of cases) (Link and Müller, 1971;Leary et al, 2000). Therefore, IgG (predominantly IgG1), and IgM are considered the major contributors to the OCB formation in the CSF (Ziemssen and Ziemssen, 2005;Ziemssen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that affects the central nervous system (CNS). The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF), but not within the serum, is a strong indicator of intrathecal antibody synthesis (Ziemssen et al, 2019) and has been considered a hallmark of MS that contributes to the diagnosis (Thompson et al, 2018). Immunoglobulin G (IgG) and IgM antibodies are major contributors to the OCBs formation in the CSF (Ziemssen and Ziemssen, 2005;Ziemssen et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF), but not within the serum, is a strong indicator of intrathecal antibody synthesis (Ziemssen et al, 2019) and has been considered a hallmark of MS that contributes to the diagnosis (Thompson et al, 2018). Immunoglobulin G (IgG) and IgM antibodies are major contributors to the OCBs formation in the CSF (Ziemssen and Ziemssen, 2005;Ziemssen et al, 2019). Elevated intrathecal IgM synthesis, but not other immunoglobulins, has been suggested to predict a worse disease evolution since the early MS stages, being associated in patients with a more disability progression and with a more aggressive form of the disease (Walsh and Tourtellotte, 1986;Villar et al, 2002Villar et al, , 2003Cepok et al, 2006;Durante et al, 2012;Beltrán et al, 2014;Frau et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Magliozzi

Mazziotti

Montibeller

et al. 2020

Front. Cell. Neurosci.

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Background: Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated. Methods: Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up. Results: A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p = 0.013). CSF IgM levels correlated with higher CSF levels of CXCL13 (p = 0.039), CCL21 (p = 0.023), interleukin 10 (IL-10) (p = 0.025), IL-12p70 (p = 0.020), CX3CL1 (p = 0.036), and CHI3L1 (p = 0.048) and were associated with earlier age of patients at diagnosis (p = 0.008), white matter lesion (WML) number (p = 0.039) and disease activity (p = 0.033) after 2 years of follow-up. Conclusion: IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Magliozzi

Mazziotti

Montibeller

et al. 2020

Front. Cell. Neurosci.

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“…Consequently, it has been shown that the ability to select appropriate responses in close succession is predicted by concentrations of serum neurofilament light chain (sNfl) ( 29 ). This is of high relevance because there are strong links between the sNfl and the integrity of the white matter structure ( 30 – 34 ), particularly in MS ( 35 , 36 ). It has been shown ( 37 ) that MS patients performed considerably worse than healthy control participants and that the deficits shown by the patients are very likely not due to simple motor deficits.…”

Section: Cognitive–cognitive Dual Tasking Assessment In the Context Omentioning

confidence: 99%

Why Cognitive–Cognitive Dual-Task Testing Assessment Should Be Implemented in Studies on Multiple Sclerosis and in Regular Clinical Practice

Beste

Ziemssen

2020

Front. Neurol.

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Cognitive impairment is prevalent and disabling in multiple sclerosis (MS) and is severely impacting quality of life (QoL). Aside its routine assessment in clinical care, it should more often be implemented as endpoint/outcome measure in clinical trials. However, a fundamental aspect—often neglected in clinical practice and clinical trials—is the assessment of multi-tasking and dual-tasking abilities. In this perspective article, we outline why, given the nature of MS, particularly the assessment of “cognitive–cognitive dual-tasking” is relevant in MS. We delineate how knowledge from basic cognitive science can inform the assessment of this important cognitive impairment in MS. Finally, we outline how the assessment of “cognitive–cognitive dual-tasking” can be implemented in computer-based screening tools (e-health devices) that can be used not only in clinical diagnostics but also in clinical trials.

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“…Several neurological-clinical domains should be part of the quantitative assessment of individual neurological FS (e.g., cognition, walking) as eg. imaging (magnetic resonance imaging, ocular coherence tomography) and electrophysiological procedures, patient-reported outcomes (PRO), new molecular (e.g., neurofilament light chain) and digital biomarkers (D'Amico et al, 2019;Ziemssen et al, 2019;Inojosa et al, 2020a). The ability to walk is an important prerequisite to participate autonomously in daily life.…”

Section: Introductionmentioning

confidence: 99%

The Dresden Protocol for Multidimensional Walking Assessment (DMWA) in Clinical Practice

et al. 2020

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Walking impairments represent one of the most debilitating symptom areas for people with multiple sclerosis (MS). It is important to detect even slightest walking impairments in order to start and optimize necessary interventions in time to counteract further progression of the disability. For this reason, a regular monitoring through gait analysis is highly necessary. At advanced stages of MS with significant walking impairment, this assessment is also necessary to optimize symptomatic treatment, choose the most suitable walking aid and plan individualized rehabilitation. In clinical practice, walking impairment is only assessed at higher levels of the disease using e.g., the Expanded Disability Status Scale (EDSS). In contrast to the EDSS, standardized functional tests such as walking speed, walking endurance and balance as well as walking quality and gait-related patient-reported outcomes allow a more holistic and sensitive assessment of walking impairment. In recent years, the MS Center Dresden has established a standardized monitoring procedure for the routine multidimensional assessment of gait and balance disorders. In the following protocol, we present the techniques and procedures for the analysis of gait and balance of people with MS at the MS Center Dresden. Patients are assessed with a multidimensional gait analysis at least once a year. This enables long-term monitoring of walking impairment, which allows early active intervention regarding further progression of disease and improves the current standard clinical practice.

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Molecular biomarkers in multiple sclerosis

Cited by 182 publications

References 144 publications

Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Why Cognitive–Cognitive Dual-Task Testing Assessment Should Be Implemented in Studies on Multiple Sclerosis and in Regular Clinical Practice

The Dresden Protocol for Multidimensional Walking Assessment (DMWA) in Clinical Practice

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