Corticosteroid-depending effects on peripheral immune cell subsets vary according to disease modifying strategies in multiple sclerosis.

Background: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.

SARS-CoV-2-Specific Immune Cytokine Profiles to mRNA, Viral Vector and Protein-Based Vaccines in Patients with Multiple Sclerosis: Beyond Interferon Gamma.

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV).

Consensus quality indicators for monitoring multiple sclerosis.

Multiple sclerosis (MS) as a chronic, degenerative autoimmune disease of the central nervous system has a longitudinal and heterogeneous course with increasing treatment options and risk profiles requiring constant monitoring of a growing number of parameters. Despite treatment guidelines, there is a lack of strategic and individualised monitoring pathways, including respective quality indicators (QIs). To address this, we systematically developed transparent, traceable, and measurable QIs for MS monitoring.

Insights from Real-World Practice: The Dynamics of SARS-CoV-2 Infections and Vaccinations in a Large German Multiple Sclerosis Cohort.

The SARS-CoV-2 pandemic profoundly impacted people with multiple sclerosis (pwMS). Disease-related aspects and demographic factors may influence vaccination rates, infection susceptibility, and severity. Despite prior research, comprehensive real-world data obtained throughout the pandemic remain limited.

Differential effects of selective versus unselective sphingosine 1-phosphate receptor modulators on T- and B-cell response to SARS-CoV-2 vaccination.

Background: Sphingosine 1-phosphat receptor modulators (S1PRMs) have been linked to attenuated immune response to SARS-CoV-2 vaccines.

Objective: To characterize differences in the immune response to SARS-CoV-2 vaccines in patients on selective versus unselective S1PRMs.

Methods: Monocentric, longitudinal study on people with multiple sclerosis (pwMS) on fingolimod (FTY), siponimod (SIP), ozanimod (OZA), or without disease-modifying therapy (DMT) following primary and booster SARS-CoV-2 vaccination.

Influence of Pre-Analytic Conditions on Quantity of Lymphocytes.

Lymphocytes are key players in the pathogenesis of multiple sclerosis and a distinct target of several immunomodulatory treatment strategies. In this study, we aim to evaluate the effect of various pre-analytic conditions on immune cell counts to conclude the relevance for clinical implications. Twenty healthy donors were assessed for the effects of distinct storage temperatures and times after blood draws, different durations of tourniquet application, body positions and varying aspiration forces during blood draws.

Pilot study on the influence of acute alcohol exposure on biophysical parameters of leukocytes.

This pilot study explores the influence of acute alcohol exposure on cell mechanical properties of steady-state and activated leukocytes conducted with real-time deformability cytometry. Nineteen healthy male volunteers were enrolled to investigate the effect of binge drinking on biophysical properties and cell counts of peripheral blood leukocytes. Each participant consumed an individualized amount of alcohol to achieve a blood alcohol concentration of 1.

Influence of exercise on quantity and deformability of immune cells in multiple sclerosis.

Objective: The study aimed to investigate the effect of exercise on immune cell count and cell mechanical properties in people with multiple sclerosis (pwMS) on different disease-modifying treatments (DMT) vs. healthy controls (HCs).

Methods: A cohort of 16 HCs and 45 pwMS, including patients with lymphopenia (alemtuzumab and fingolimod) as well as increased lymphocyte counts (natalizumab), was evaluated for exercise-mediated effects on immune cell counts and lymphocyte deformability.

Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis.

Background: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk.

Objectives: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab.

Methods: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line.

The need for a strategic therapeutic approach: multiple sclerosis in check.

Multiple sclerosis (MS) is the most common chronic autoimmune neurological disease. Its therapeutic management has drastically evolved in the recent years with the development of specific disease-modifying therapies (DMTs). Together with the established injectables, oral and intravenous alternatives are now available for MS patients with significant benefits to modulate the disease course.

Lymphocyte Counts and Multiple Sclerosis Therapeutics: Between Mechanisms of Action and Treatment-Limiting Side Effects.

Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common side effect of nearly every MS therapeutic agent is lymphopenia, which can be both beneficial and, in some cases, treatment-limiting. A sound knowledge of the underlying mechanism of action of the selected agent is required in order to understand treatment-associated changes in white blood cell counts, as well as monitoring consequences.

Drug and Neurofilament Levels in Serum and Breastmilk of Women With Multiple Sclerosis Exposed to Natalizumab During Pregnancy and Lactation.

Objective: To determine the transfer of the monoclonal antibody natalizumab into breastmilk and to evaluate drug and serum neurofilament light chain ((s)NfL) levels in natalizumab exposed pregnancies and lactation periods.

Methods: Eleven women with relapsing remitting multiple sclerosis treated with natalizumab during pregnancy and lactation were included in this study. Breastmilk samples were collected up to 302 days after delivery and analyzed for natalizumab concentration and NfL.

Natalizumab Pharmacokinetics and -Dynamics and Serum Neurofilament in Patients With Multiple Sclerosis.

Natalizumab (NAT) is a high-efficacy treatment for relapsing remitting multiple sclerosis (RRMS). However, it is associated with an increased risk of progressive multifocal leukoencephalopathy that sometimes requires treatment cessation with a risk of returning disease activity. The aim of this study was to characterize the pharmacokinetics and -dynamics as well as neurodestruction marker serum neurofilament light chain (sNfL) in patients with RRMS and secondary progressive MS (SPMS) stopping NAT in correlation to clinical data.

Should We Use Clinical Tools to Identify Disease Progression?

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted.

No Impact of Long-Term Fingolimod Treatment on Fecal Secretory Immunoglobulin A Levels in Patients With Multiple Sclerosis.

Background: Fingolimod (FTY) is a sphingosine 1 phosphate (S1P) agonist with significant effects on immune cell distribution used as an effective disease modifying therapy in multiple sclerosis (MS) patients. Animal studies have demonstrated that a dysregulation of egress of murine secretory Immunglobulin A (sIgA)+ plasmablasts from Peyer's patches in FTY-treated mice reduced fecal sIgA levels. Alterations in intestinal levels of sIgA could modify the gut microbiome and homeostasis in humans.

The role of TH17 cells in multiple sclerosis: Therapeutic implications.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where immunopathology is thought to be mediated by myelin-reactive CD4 T helper (TH) cells. The TH cells most commonly implicated in the pathogenesis of the disease are of TH1 and TH17 lineage, which are defined by the production of interferon-γ and interleukin-17, respectively. Moreover, there is emerging evidence for the involvement of TH17.

A focus on secondary progressive multiple sclerosis (SPMS): challenges in diagnosis and definition.

Secondary progressive multiple sclerosis (SPMS) is the second most common form of multiple sclerosis (MS). One in two relapse remitting multiple sclerosis (RRMS) patients will develop SPMS within 15 years and up to two-thirds after 30 years, leading to a progressive decrease of neurological function and limitation of daily activities. Nevertheless, the SPMS diagnosis is often established retrospectively and delayed up to 3 years due to several patient- and clinician-related factors.

Early central vs. peripheral immunological and neurobiological effects of fingolimod-a longitudinal study.

Fingolimod (FTY) is known to have multiple effects on the immune system and the central nervous system (CNS) in patients with multiple sclerosis (MS). In this study, we evaluated the immunological and neurobiological effects of FTY in MS. Blood and cerebrospinal fluid (CSF) samples were collected from 15 MS patients before first FTY administration and after 4 months of FTY therapy.

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS.

Objective: To evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.

Methods: We investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.

Nonwalking response to fampridine in patients with multiple sclerosis in a real-world setting.

Objectives: Mobility impairments constitute a long-term burden in patients with multiple sclerosis (MS). Currently there is evidence that the drug fampridine may improve nonwalking symptoms in MS patients. The main objective of this study is to analyze whether participants showing a beneficial walking response to fampridine, also show a positive response in nonwalking assessments in a real-world clinical setting.

Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up.

Natalizumab inhibits the transmigration of immune cells across the blood-brain barrier thus inhibiting inflammation in the central nervous system. Generally, this blockade at the blood-brain barrier has significant influence on the circulating lymphocytes. Up to date, only short-term data on peripheral blood parameters are available which are mostly from controlled clinical trials and not from real-world experience.

Real World Lab Data: Patterns of Lymphocyte Counts in Fingolimod Treated Patients.

Objective: Fingolimod is approved for the treatment of highly active relapsing remitting multiple sclerosis (MS) patients and acts by its unique mechanism of action via sphingosine-1-phosphate receptor-modulation. Although fingolimod-associated lymphopenia is a well-known phenomenon, the exact cause for the intra- and inter-individual differences of the fluctuation of lymphocyte count and its subtypes is still subject of debate. In this analysis, we aim to estimate the significance of the individual variation of distinct lymphocyte subsets for differences in absolute lymphocyte decrease in fingolimod treated patients and discuss how different lymphocyte subset patterns are related to clinical presentation in a long-term real life setting.