Publications by authors named "Luisa Klotz"

Objective: In this multicentric study, we were interested in the vision-related quality of life and its association with visual impairment in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in comparison to multiple sclerosis (MS) and healthy controls.

Methods: We analysed extracted data from the German NEMOS registry including National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores, high and low contrast visual acuity (HCVA, LCVA), visually evoked potentials (VEP) and the scores for the expanded disability status scale (EDSS) and other neurological tests which assessed their disease-related impairment. The mean follow-up time of our patients was 1.

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Background And Objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.

Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints.

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Background: A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (T) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since T and anti-inflammatory (M2-type) macrophages were found to enhance stroke recovery, we hypothesized that CLA-supplementation might improve stroke recovery via immune modulatory effects.

Methods: Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice ( = 37, sham  = 10).

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Article Synopsis
  • Eculizumab (ECU) has shown effectiveness in preventing attacks in patients with aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (NMOSDs) during a retrospective analysis in clinical settings between 2014 and 2022.
  • A total of 52 patients were studied, with 88% being attack-free during treatment, and the annualized attack rate significantly decreased from 1.0 to 0.
  • While common side effects included serious infections, five patients died from various complications, indicating a need for careful monitoring during long-term ECU therapy.
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Background: Data on cognition in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited to studies with small sample sizes. Therefore, we aimed to analyse the extent, characteristics and the longitudinal course of potential cognitive deficits in patients with MOGAD.

Methods: The CogniMOG-Study is a prospective, longitudinal and multicentre observational study of 113 patients with MOGAD.

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Demyelination due to autoreactive T cells and inflammation in the central nervous system are principal features of multiple sclerosis (MS), a chronic and highly disabling human disease affecting brain and spinal cord. Here, we show that treatment with apelin, a secreted peptide ligand for the G protein-coupled receptor APJ/Aplnr, is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Apelin reduces immune cell entry into the brain, delays the onset and reduces the severity of EAE.

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Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). MS patients have elevated titers of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T-cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire compared to controls.

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Progressive multifocal leukoencephalopathy (PML) has been associated with different forms of immune compromise. This study analyzes the chemokine signals and attracted immune cells in cerebrospinal fluid (CSF) during PML to define immune cell subpopulations relevant for the PML immune response. In addition to chemokines that indicate a general state of inflammation, like CCL5 and CXCL10, the CSF of PML patients specifically contains CCL2 and CCL4.

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5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients.

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Article Synopsis
  • Managing multiple sclerosis is challenging due to the varying symptoms and disease progressions in patients, leading to difficulty in individualized treatment selection.
  • Researchers identified three unique blood immune profiles (endophenotypes) in early multiple sclerosis patients using advanced techniques, which correspond to different disease progression patterns—one focusing on inflammation and another on early structural damage.
  • The study suggests that understanding a patient's specific immune profile before starting treatment could help predict disease progression and support more personalized treatment strategies, as certain therapies may be less effective for some endophenotypes.
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Neutrophils, the most abundant white blood cells in the human circulation, play crucial roles in various diseases, including kidney disease. Traditionally viewed as short-lived pro-inflammatory phagocytes that release reactive oxygen species, cytokines and neutrophil extracellular traps, recent studies have revealed their complexity and heterogeneity, thereby challenging this perception. Neutrophils are now recognized as transcriptionally active cells capable of proliferation and reverse migration, displaying phenotypic and functional heterogeneity.

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Article Synopsis
  • The study focused on understanding how disability accumulates in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD), examining factors like disease duration, attack frequency, and age.* -
  • Data from 483 patients indicated that NMOSD patients reached significant disability milestones much sooner than MOGAD patients, despite similar attack rates; older age at symptom onset was linked to higher disability risk.* -
  • Overall, NMOSD and MOGAD exhibit different patterns of disability progression, with MOGAD being less severe, and recent research has enhanced awareness and treatment strategies, positively impacting patient outcomes.*
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Background: Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.

Objectives: Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease causing axonal degeneration and demyelination. Exercise in mice with active monophasic experimental autoimmune encephalomyelitis (EAE) attenuates disease severity associated with diverse impacts on T cell-mediated immunity. However, studies have so far focused on preventive approaches.

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Article Synopsis
  • - This manuscript offers practical advice for treating acute attacks and preventing future episodes of neuromyelitis optica spectrum disorders (NMOSD), an autoimmune disease that severely impacts the central nervous system, primarily affecting vision and mobility.
  • - The study highlights the importance of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) as a key diagnostic marker and contributor to NMOSD, with recent advancements leading to four new approved preventive therapies: eculizumab, ravulizumab, inebilizumab, and satralizumab, which may replace older treatments.
  • - The Neuromyelitis Optica Study Group (NEMOS) presents a consensus on current NMOSD therapies and practical
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Influenza A virus (IAV), like any other virus, provokes considerable modifications of its host cell's metabolism. This includes a substantial increase in the uptake as well as the metabolization of glucose. Although it is known for quite some time that suppression of glucose metabolism restricts virus replication, the exact molecular impact on the viral life cycle remained enigmatic so far.

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Clinical symptom worsening in patients with multiple sclerosis (MS) is driven by inflammation compartmentalized within the CNS, which results in chronic neuronal damage owing to insufficient repair mechanisms. The term 'smouldering inflammation' summarizes the biological aspects underlying this chronic, non-relapsing and immune-mediated mechanism of disease progression. Smouldering inflammation is likely to be shaped and sustained by local factors in the CNS that account for the persistence of this inflammatory response and explain why current treatments for MS do not sufficiently target this process.

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Growth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose-dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose-dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells.

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Background: Western lifestyle has been associated with an increase in relapsing-remitting multiple sclerosis (RRMS). In mice, dietary wheat amylase-trypsin inhibitors (ATIs) activate intestinal myeloid cells and augment T cell-mediated systemic inflammation.

Objective: The aim of this study was to assess whether a wheat- and thus ATI-reduced diet might exert beneficial effects in RRMS patients with modest disease activity.

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To assess the relative efficacy of disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) including newer therapies (ozanimod, ponesimod, ublituximab) using network meta-analysis (NMA). Bayesian NMAs for annualised relapse rate (ARR) and time to 3-month and 6-month confirmed disability progression (3mCDP and 6mCDP) were conducted. For each outcome, the three most efficacious treatments versus placebo were monoclonal antibody (mAb) therapies: alemtuzumab, ofatumumab, and ublituximab for ARR; alemtuzumab, ocrelizumab, and ofatumumab for 3mCDP; and alemtuzumab, natalizumab, and either ocrelizumab or ofatumumab (depending on the CDP definition used for included ofatumumab trials) for 6mCDP.

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Despite the large number of immunomodulatory or immunosuppressive treatments available to treat relapsing-remitting multiple sclerosis (MS), treatment of the progressive phase of the disease has not yet been achieved. This lack of successful treatment approaches is caused by our poor understanding of the mechanisms driving disease progression. Emerging concepts suggest that a combination of persisting focal and diffuse inflammation within the CNS and a gradual failure of compensatory mechanisms, including remyelination, result in disease progression.

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Article Synopsis
  • The term 'neuromyelitis optica spectrum disorders' (NMOSD) encompasses several related conditions, including aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica (NMO) and other syndromes lacking AQP4-IgG.
  • NMOSD is now recognized as a distinct disorder, separate from multiple sclerosis (MS), due to differences in their causes, clinical presentation, treatments, and outcomes.
  • The article series includes updated guidelines for diagnosing NMOSD and differentiating it from similar conditions, such as MOG antibody-associated diseases, as well as recommendations for the latest treatment options available.
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