Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy

Heming, M.; Wiendl, Heinz

doi:10.1073/pnas.2221544120

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…The disease begins earlier than current diagnostic criteria can detect. It affects the entire central nervous system and not just the white matter, as the original terminflammatory demyelinating disorder-suggests [3]. It is characterized by a very heterogeneous course of the disease, which is represented by relapse-associated neurological deterioration, but also by an increase in disability that is independent of relapse [4].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

2024

Infect Dis Ther

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CoV--a decisive • VitD deficiency-risk factor pathology Vitamin D SARS-CoV-2-Virus suppl.Hans-Klaus Goischke ( 2024) SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation? rate was significantly lower than with values below or with deficiency [17]. Current data suggest a protective role for VitD, particularly with a lower risk of intensive care unit admission and a reduced risk of death [18,19]. In addition, the occurrence of Long-Covid is an aspect of implementing this simple, effective, safe and costeffective therapy with a broad therapeutic window for the prevention and treatment of COVID-19 disease [20-22]. Although there is still no indisputable evidence that Vit D supplementation (VitD suppl.) reduces the risk of SARSCov-2 infection in healthy individuals, there is collective evidence that it benefits vulnerable individuals [23]. PwMS with comorbidities, psychiatric illnesses, hypertension, obesity (an increased BMI may correlate with a severe course of Covid-19), age > 50 years, severe disability and methylprednisolone boost therapy as well as some DMTs (disease-modifying therapies) have a higher risk of infection and an increased risk of severe COVID-19 courses [24-26]. Infections (SARS-COV-2) can increase MS symptoms (pseudo-relapses) or cause real relapses [27]. In post-COVID syndrome (Long Covid), one in eight patients presents with symptoms such as fatigue, shortness of breath, cough, joint pain, chest pain, muscle pain, headache and paresthesia in the limbs after at least 3 months. The latter can also occur in PwMS per se [28,29]. If vitamin D administration results in a lower risk of infection, severity of illness with admission to the intensive care unit or a reduced risk of death in people at risk, Long-Covid occurs less frequently [18,19,21,22,[30][31][32][33], it is not ethically justifiable to withhold high dose vitamin-D administration from people at risk.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

2024

Infect Dis Ther

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“…More indepth insights into the effector program of brain-homing CD4 + T cells in people with MS are needed to better understand which subsets are triggered and how these affect the BBB as an initial event in the disease course [3,4]. The obtained knowledge can help to fine-tune and personalize the use of currently available T-cell-directed treatments and to develop more refined therapeutic strategies that only target the disease-relevant T-cell subsets [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Differential Runx3, Eomes, and T‐bet expression subdivides MS‐associated CD4⁺ T cells with brain‐homing capacity

Hoeks,

Puijfelik,

Koetzier

et al. 2023

Eur J Immunol

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Multiple sclerosis (MS) is a common and devastating chronic inflammatory disease of the CNS. CD4+ T cells are assumed to be the first to cross the blood–central nervous system (CNS) barrier and trigger local inflammation. Here, we explored how pathogenicity‐associated effector programs define CD4+ T cell subsets with brain‐homing ability in MS. Runx3‐ and Eomes‐, but not T‐bet‐expressing CD4+ memory cells were diminished in the blood of MS patients. This decline reversed following natalizumab treatment and was supported by a Runx3+Eomes+T‐bet− enrichment in cerebrospinal fluid samples of treatment‐naïve MS patients. This transcription factor profile was associated with high granzyme K (GZMK) and CCR5 levels and was most prominent in Th17.1 cells (CCR6+CXCR3+CCR4−/dim). Previously published CD28− CD4 T cells were characterized by a Runx3+Eomes−T‐bet+ phenotype that coincided with intermediate CCR5 and a higher granzyme B (GZMB) and perforin expression, indicating the presence of two separate subsets. Under steady‐state conditions, granzyme Khigh Th17.1 cells spontaneously passed the blood–brain barrier in vitro. This was only found for other subsets including CD28− cells when using inflamed barriers. Altogether, CD4+ T cells contain small fractions with separate pathogenic features, of which Th17.1 seems to breach the blood–brain barrier as a possible early event in MS.

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Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy

Cited by 2 publications

References 23 publications

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

Differential Runx3, Eomes, and T‐bet expression subdivides MS‐associated CD4⁺ T cells with brain‐homing capacity

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Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy

Cited by 2 publications

References 23 publications

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

SARS-CoV-2 Infection and Multiple Sclerosis: Proactive Approach in a Vulnerable Patient Group through Daily Vitamin D Supplementation?

Differential Runx3, Eomes, and T‐bet expression subdivides MS‐associated CD4+ T cells with brain‐homing capacity

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Differential Runx3, Eomes, and T‐bet expression subdivides MS‐associated CD4⁺ T cells with brain‐homing capacity