18 results on '"Schulte-Mecklenbeck A"'
Search Results
2. Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry
- Author
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Michael Heming, Louisa Müller-Miny, Leoni Rolfes, Andreas Schulte-Mecklenbeck, Tobias J. Brix, Julian Varghese, Marc Pawlitzki, Hermann Pavenstädt, Martin A. Kriegel, Catharina C. Gross, Heinz Wiendl, and Gerd Meyer zu Hörste
- Subjects
Cerebrospinal fluid ,Connective tissue disease ,Systemic lupus erythematosus ,Flow cytometry ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Objective Neurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without neurological manifestation. Methods Using flow cytometry, we retrospectively investigated paired cerebrospinal fluid (CSF) and blood samples of 28 CTD patients without neurological manifestation, 38 CTD patients with neurological manifestation (N-CTD), 38 non-inflammatory controls, and 38 multiple sclerosis (MS) patients, a paradigmatic primary neuroinflammatory disease. Results We detected an expansion of plasma cells in the blood of both N-CTD and CTD compared to non-inflammatory controls and MS. Blood plasma cells alone distinguished the clinically similar entities N-CTD and MS with high discriminatory performance (AUC: 0.81). Classical blood monocytes indicated higher disease activity in systemic lupus erythematosus (SLE) patients. Surprisingly, immune cells in the CSF did not differ significantly between N-CTD and CTD, while CD4+ T cells and the CD4+/CD8+ ratio were elevated in the blood of N-CTD compared to CTD. Several B cell-associated parameters partially overlapped in the CSF in MS and N-CTD. We built a machine learning model that distinguished N-CTD from MS with high discriminatory power using either blood or CSF. Conclusion We here find that blood flow cytometry alone surprisingly suffices to distinguish CTD with neurological manifestations from clinically similar entities, suggesting that a rapid blood test could support clinicians in the differential diagnosis of N-CTD.
- Published
- 2023
- Full Text
- View/download PDF
3. Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.
- Author
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Dambietz, Christine, Heming, Michael, Brix, Tobias J., Schulte-Mecklenbeck, Andreas, Tepasse, Phil-Robin, Gross, Catharina C., Trebicka, Jonel, Wiendl, Heinz, and zu Hörste, Gerd Meyer
- Subjects
KILLER cells ,CYTOTOXIC T cells ,MENINGITIS ,HIV infections ,BACTERIAL meningitis ,CEREBROSPINAL fluid - Abstract
Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights Into Inflammatory Neuropathies
- Author
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Michael Heming, Andreas Schulte-Mecklenbeck, Tobias Brix, Jolien Wolbert, Tillmann Ruland, Luisa Klotz, Sven G. Meuth, Catharina C. Gross, Heinz Wiendl, and Gerd Meyer zu Hörste
- Subjects
inflammatory neuropathies ,Guillain-Barré syndrome ,chronic inflammatory demyelinating polyneuropathy ,immune cell profile ,cerebrospinal fluid ,flow cytometry ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies.Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63).Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies.Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies.
- Published
- 2019
- Full Text
- View/download PDF
5. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions
- Author
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Catharina C. Gross, Marc Pawlitzki, Andreas Schulte-Mecklenbeck, Leoni Rolfes, Tobias Ruck, Petra Hundehege, Heinz Wiendl, Michael Herty, and Sven G. Meuth
- Subjects
cns inflammation ,autoimmune diseases ,multiple sclerosis ,susac syndrome ,cerebrospinal fluid ,central nervous system ,flow cytometry ,markov chain model ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The central nervous system (CNS) is an immune-privileged compartment that is separated from the circulating blood and the peripheral organs by the blood−brain and the blood−cerebrospinal fluid (CSF) barriers. Transmigration of lymphocyte subsets across these barriers and their activation/differentiation within the periphery and intrathecal compartments in health and autoinflammatory CNS disease are complex. Mathematical models are warranted that qualitatively and quantitatively predict the distribution and differentiation stages of lymphocyte subsets in the blood and CSF. Here, we propose a probabilistic mathematical model that (i) correctly reproduces acquired data on location and differentiation states of distinct lymphocyte subsets under homeostatic and neuroinflammatory conditions, (ii) provides a quantitative assessment of differentiation and transmigration rates under these conditions, (iii) correctly predicts the qualitative behavior of immune-modulating therapies, (iv) and enables simulation-based prediction of distribution and differentiation stages of lymphocyte subsets in the case of limited access to biomaterial. Taken together, this model might reduce future measurements in the CSF compartment and allows for the assessment of the effectiveness of different immune-modulating therapies.
- Published
- 2020
- Full Text
- View/download PDF
6. Cerebrospinal fluid flow cytometry distinguishes psychosis spectrum disorders from differential diagnoses
- Author
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Gerd Meyer zu Hörste, Saskia Räuber, Tillmann Ruland, Tim Hahn, Andreas Schulte-Mecklenbeck, Sven G. Meuth, Jonathan Repple, Catharina C. Gross, Heinz Wiendl, Rebecca Kuelby, Udo Dannlowski, Nico Melzer, Michael Heming, Volker Arolt, and Bernhard T. Baune
- Subjects
Autoimmune encephalitis ,Psychosis ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Flow Cytometry ,medicine.disease ,Flow cytometry ,Diagnosis, Differential ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Cerebrospinal fluid ,Immune system ,Psychotic Disorders ,Immunology ,medicine ,Encephalitis ,Humans ,Medical diagnosis ,business ,Molecular Biology ,Cytometry ,Cerebrospinal Fluid ,Retrospective Studies - Abstract
Psychotic disorders are common and disabling mental conditions. The relative importance of immune-related mechanisms in psychotic disorders remains subject of debate. Here, we present a large-scale retrospective study of blood and cerebrospinal fluid (CSF) immune cell profiles of psychosis spectrum patients. We performed basic CSF analysis and multi-dimensional flow cytometry of CSF and blood cells from 59 patients with primary psychotic disorders (F20, F22, F23, and F25) in comparison to inflammatory (49 RRMS and 16 NMDARE patients) and non-inflammatory controls (52 IIH patients). We replicated the known expansion of monocytes in the blood of psychosis spectrum patients, that we identified to preferentially affect classical monocytes. In the CSF, we found a relative shift from lymphocytes to monocytes, increased protein levels, and evidence of blood–brain barrier disruption in psychosis. In fact, these CSF features confidently distinguished autoimmune encephalitis from psychosis despite similar (initial) clinical features. We then constructed machine learning models incorporating blood and CSF parameters and demonstrated their superior ability to differentiate psychosis from non-inflammatory controls compared to individual parameters. Multi-dimensional and multi-compartment immune cell signatures can thus support the diagnosis of psychosis spectrum disorders with the potential to accelerate diagnosis and initiation of therapy.
- Published
- 2021
7. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions
- Author
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Leoni Rolfes, Tobias Ruck, Michael Herty, Andreas Schulte-Mecklenbeck, Sven G. Meuth, Petra Hundehege, Marc Pawlitzki, Catharina C. Gross, and Heinz Wiendl
- Subjects
Male ,Intrathecal ,multiple sclerosis ,lcsh:Chemistry ,Cerebrospinal fluid ,Cell Movement ,Central Nervous System Diseases ,Homeostasis ,Child ,lcsh:QH301-705.5 ,Spectroscopy ,medicine.diagnostic_test ,General Medicine ,Middle Aged ,Computer Science Applications ,medicine.anatomical_structure ,ddc:540 ,Female ,Disease Susceptibility ,Lymphocyte subsets ,Adult ,Adolescent ,Central nervous system ,Biology ,Models, Biological ,Susac syndrome ,Article ,Catalysis ,cerebrospinal fluid ,Immunophenotyping ,Flow cytometry ,Inorganic Chemistry ,Young Adult ,medicine ,Humans ,Compartment (development) ,autoimmune diseases ,Lymphocyte Count ,Physical and Theoretical Chemistry ,Molecular Biology ,Inflammation ,Multiple sclerosis ,flow cytometry ,Organic Chemistry ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,central nervous system ,Lymphocyte Subsets ,CNS inflammation ,lcsh:Biology (General) ,lcsh:QD1-999 ,Markov chain model ,Neuroscience ,Biomarkers - Abstract
The central nervous system (CNS) is an immune-privileged compartment that is separated from the circulating blood and the peripheral organs by the blood&ndash, brain and the blood&ndash, cerebrospinal fluid (CSF) barriers. Transmigration of lymphocyte subsets across these barriers and their activation/differentiation within the periphery and intrathecal compartments in health and autoinflammatory CNS disease are complex. Mathematical models are warranted that qualitatively and quantitatively predict the distribution and differentiation stages of lymphocyte subsets in the blood and CSF. Here, we propose a probabilistic mathematical model that (i) correctly reproduces acquired data on location and differentiation states of distinct lymphocyte subsets under homeostatic and neuroinflammatory conditions, (ii) provides a quantitative assessment of differentiation and transmigration rates under these conditions, (iii) correctly predicts the qualitative behavior of immune-modulating therapies, (iv) and enables simulation-based prediction of distribution and differentiation stages of lymphocyte subsets in the case of limited access to biomaterial. Taken together, this model might reduce future measurements in the CSF compartment and allows for the assessment of the effectiveness of different immune-modulating therapies.
- Published
- 2020
8. Immune cell profiling in the cerebrospinal fluid of patients with primary angiitis of the central nervous system reflects the heterogeneity of the disease
- Author
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Catharina C. Gross, Carolin Beuker, Andreas Schulte-Mecklenbeck, Heinz Wiendl, Jens Minnerup, Nico Melzer, Gerd Meyer zu Hörste, Daniel Strunk, Kristin S. Golombeck, Antje Schmidt, and Sven G. Meuth
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,T-Lymphocytes ,Immunology ,Central nervous system ,Disease ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cerebrospinal fluid ,medicine ,Humans ,Immunology and Allergy ,Vasculitis, Central Nervous System ,Aged ,030203 arthritis & rheumatology ,B-Lymphocytes ,Immunity, Cellular ,biology ,medicine.diagnostic_test ,business.industry ,Multiple sclerosis ,Middle Aged ,medicine.disease ,Pathophysiology ,Killer Cells, Natural ,medicine.anatomical_structure ,Neurology ,biology.protein ,Female ,Neurology (clinical) ,Antibody ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Primary angiitis of the central nervous system (PACNS) is a rare and heterogeneous inflammatory disease of the CNS vasculature with poorly understood pathophysiology. Comprehensive immune-cell phenotyping revealed increased frequencies of leukocytes in the cerebrospinal fluid (CSF) of PACNS patients compared to patients with multiple sclerosis, ischemic stroke, and somatoform disorders (n = 18 per group). Changes in the intrathecal immune-cell profile were heterogeneous in PACNS. While proportions of T-cell subsets remained unaltered, some PACNS patients showed a shift toward NK- or B cells. Intrathecal immunoglobulin synthesis was observed in a subgroup of PACNS patients with an increased frequency of antibody producing plasma cells.
- Published
- 2018
9. Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments.
- Author
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Repple, Jonathan, Haessner, Svea, Johnen, Andreas, Landmeyer, Nils C., Schulte-Mecklenbeck, Andreas, Pawlitzki, Marc, Wiendl, Heinz, and Meyer zu Hörste, Gerd
- Subjects
METHADONE hydrochloride ,KILLER cells ,MAGNETIC resonance imaging ,CENTRAL nervous system ,CEREBROSPINAL fluid - Abstract
Background: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone–use and –abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. Case presentation: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. Conclusion: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
10. Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke
- Author
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Andreas Schulte-Mecklenbeck, Heinz Wiendl, Timo Wirth, Luisa Klotz, Carolin Beuker, Sven G. Meuth, Ilka Kleffner, Catharina C. Gross, Wiebke Hansen, Antje Schmidt-Pogoda, Marvin Hartwig, and Jens Minnerup
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Cell ,Medizin ,Inflammation ,Monocytes ,Flow cytometry ,Brain Ischemia ,Immunophenotyping ,03 medical and health sciences ,Leukocyte Count ,0302 clinical medicine ,Cerebrospinal fluid ,Immune system ,Parenchyma ,medicine ,Leukocytes ,Humans ,030212 general & internal medicine ,Lymphocytes ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Middle Aged ,Stroke ,medicine.anatomical_structure ,Neurology ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Background and purpose Post-ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. Methods In a retrospective cohort study, we performed extensive immune-cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow-up imaging. Results Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non-significantly elevated (1.76 vs. 0.50 cells/μL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. Conclusions Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke.
- Published
- 2018
11. Cerebrospinal Fluid Concentrations of Neuronal Proteins Are Reduced in Primary Angiitis of the Central Nervous System
- Author
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Tillmann Ruland, Jolien Wolbert, Michael G. Gottschalk, Simone König, Andreas Schulte-Mecklenbeck, Jens Minnerup, Sven G. Meuth, Catharina C. Groß, Heinz Wiendl, and Gerd Meyer zu Hörste
- Subjects
0301 basic medicine ,Central nervous system ,CSF ,Disease ,Proteomics ,lcsh:RC346-429 ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Autoimmune vasculitis ,medicine ,lcsh:Neurology. Diseases of the nervous system ,mass spectrometry ,medicine.diagnostic_test ,business.industry ,flow cytometry ,amyloid-beta A4 protein ,030104 developmental biology ,medicine.anatomical_structure ,Functional annotation ,Amyloid Beta A4 Protein ,Neurology ,Immunology ,PACNS ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis limited to the CNS often causing substantial disability. Understanding of this disease is impaired by the lack of available biomaterial. Here, we collected cerebrospinal fluid (CSF) from patients with PACNS and matched controls and performed unbiased proteomics profiling using ion mobility mass spectrometry to identify novel disease mechanisms and candidate biomarkers. We identified 14 candidate proteins, including amyloid-beta A4 protein (APP), with reduced abundance in the CSF of PACNS patients and validated APP by Enzyme-linked Immunosorbent Assay (ELISA) in an extended cohort of patients with PACNS. Subsequent functional annotation surprisingly suggested neuronal pathology rather than immune activation in PACNS. Our study is the first to employ mass spectrometry to local immune reactions in PACNS and it identifies candidates such as APP with pathogenic relevance in PACNS to improve patient care in the future.
- Published
- 2018
- Full Text
- View/download PDF
12. Neurocognitive decline in<scp>HIV</scp>patients is associated with ongoing T‐cell activation in the cerebrospinal fluid
- Author
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Tilman Schneider-Hohendorf, Doris Reichelt, Andreas Schulte-Mecklenbeck, Catharina C. Gross, Sven G. Meuth, Heinz Wiendl, Oliver Grauer, Hubertus Lohmann, Ute Grüneberg, and Ingo W. Husstedt
- Subjects
Cart ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,T cell ,Magnetic resonance imaging ,Flow cytometry ,Cerebrospinal fluid ,medicine.anatomical_structure ,Downregulation and upregulation ,Immunology ,medicine ,Neurology (clinical) ,business ,Neurocognitive ,Research Articles ,CD8 - Abstract
Objective HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND. Methods In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples to determine the expression of HLA-DR and programmed death-1 (PD-1) on CD4+ and CD8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF, classification of HAND and severity of magnetic resonance imaging (MRI) signal abnormalities. Results In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD4/CD8-ratios and increased frequencies of HLA-DR expressing CD4+ and CD8+ T cells reaching the highest values in the CSF samples. Importantly, HLA-DR upregulation was still detectable in virologically suppressed HIV patients. Further, T-cell subpopulation analysis of 40 HIV patients showed a significant shift from naive to effector memory (EM) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD-1 was significantly increased on CD4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations. Interpretation The CD4/CD8 ratio, the proportion of EM to naive T cells and the immune activation profile of CD4+ and CD8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration.
- Published
- 2015
13. Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies.
- Author
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Langenbruch, Lisa, Bleß, Laurens, Schulte‐Mecklenbeck, Andreas, Sundermann, Benedikt, Brix, Tobias, Elger, Christian E., Melzer, Nico, Wiendl, Heinz, Meuth, Sven G., Gross, Catharina C., and Kovac, Stjepana
- Subjects
TEMPORAL lobe epilepsy ,CEREBROSPINAL fluid ,GLUTAMATE decarboxylase ,ETIOLOGY of diseases ,T cells - Abstract
Inflammation plays a role in the pathogenesis of immune‐mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age‐matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65‐kDa isoform of glutamic acid decarboxylase (GAD65‐LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen–DR isotype (HLA‐DR)‐expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14lowCD16+ cells in the PB and blood/CSF‐barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65‐LE differed from other TLE patients by increased proportions of HLA‐DR–expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
14. Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke.
- Author
-
Schulte‐Mecklenbeck, A., Beuker, C., Wirth, T., Hartwig, M., Schmidt‐Pogoda, A., Klotz, L., Wiendl, H., Meuth, S. G., Gross, C. C., Minnerup, J., Kleffner, I., and Hansen, W.
- Subjects
- *
CEREBROSPINAL fluid , *STROKE , *CELL analysis , *LEUCOCYTES , *IMMUNOPHENOTYPING , *CELLS - Abstract
Background and purpose: Post‐ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. Methods: In a retrospective cohort study, we performed extensive immune‐cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow‐up imaging. Results: Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non‐significantly elevated (1.76 vs. 0.50 cells/μL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. Conclusions: Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
15. Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights Into Inflammatory Neuropathies.
- Author
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Heming, Michael, Schulte-Mecklenbeck, Andreas, Brix, Tobias, Wolbert, Jolien, Ruland, Tillmann, Klotz, Luisa, Meuth, Sven G., Gross, Catharina C., Wiendl, Heinz, and Meyer zu Hörste, Gerd
- Subjects
CELLULAR immunity ,CEREBROSPINAL fluid ,NEUROLOGICAL disorders ,FLOW cytometry ,MULTIPLE sclerosis - Abstract
Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies. Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63). Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies. Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
16. Immune cell profiling in the cerebrospinal fluid of patients with primary angiitis of the central nervous system reflects the heterogeneity of the disease.
- Author
-
Strunk, Daniel, Schulte-Mecklenbeck, Andreas, Golombeck, Kristin S., Meyer zu Hörste, Gerd, Melzer, Nico, Beuker, Carolin, Schmidt, Antje, Wiendl, Heinz, Meuth, Sven G., Gross, Catharina C., and Minnerup, Jens
- Subjects
- *
CEREBROSPINAL fluid , *VASCULITIS , *CENTRAL nervous system , *HETEROGENEITY , *MULTIPLE sclerosis , *PATIENTS - Abstract
Primary angiitis of the central nervous system (PACNS) is a rare and heterogeneous inflammatory disease of the CNS vasculature with poorly understood pathophysiology. Comprehensive immune-cell phenotyping revealed increased frequencies of leukocytes in the cerebrospinal fluid (CSF) of PACNS patients compared to patients with multiple sclerosis, ischemic stroke, and somatoform disorders (n = 18 per group). Changes in the intrathecal immune-cell profile were heterogeneous in PACNS. While proportions of T-cell subsets remained unaltered, some PACNS patients showed a shift toward NK- or B cells. Intrathecal immunoglobulin synthesis was observed in a subgroup of PACNS patients with an increased frequency of antibody producing plasma cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
17. Cerebrospinal Fluid Concentrations of Neuronal Proteins Are Reduced in Primary Angiitis of the Central Nervous System.
- Author
-
Ruland, Tillmann, Wolbert, Jolien, Gottschalk, Michael G., König, Simone, Schulte-Mecklenbeck, Andreas, Minnerup, Jens, Meuth, Sven G., Groß, Catharina C., Wiendl, Heinz, and zu Hörste, Gerd Meyer
- Subjects
CEREBROSPINAL fluid ,VASCULITIS ,MASS spectrometry - Abstract
Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis limited to the CNS often causing substantial disability. Understanding of this disease is impaired by the lack of available biomaterial. Here, we collected cerebrospinal fluid (CSF) from patients with PACNS and matched controls and performed unbiased proteomics profiling using ion mobility mass spectrometry to identify novel disease mechanisms and candidate biomarkers. We identified 14 candidate proteins, including amyloid-beta A4 protein (APP), with reduced abundance in the CSF of PACNS patients and validated APP by Enzyme-linked Immunosorbent Assay (ELISA) in an extended cohort of patients with PACNS. Subsequent functional annotation surprisingly suggested neuronal pathology rather than immune activation in PACNS. Our study is the first to employ mass spectrometry to local immune reactions in PACNS and it identifies candidates such as APP with pathogenic relevance in PACNS to improve patient care in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
18. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions.
- Author
-
Gross, Catharina C., Pawlitzki, Marc, Schulte-Mecklenbeck, Andreas, Rolfes, Leoni, Ruck, Tobias, Hundehege, Petra, Wiendl, Heinz, Herty, Michael, and Meuth, Sven G.
- Subjects
CENTRAL nervous system physiology ,LYMPHOCYTE subsets ,CENTRAL nervous system ,BEHAVIOR therapy ,OLIGODENDROGLIA ,CEREBROSPINAL fluid - Abstract
The central nervous system (CNS) is an immune-privileged compartment that is separated from the circulating blood and the peripheral organs by the blood–brain and the blood–cerebrospinal fluid (CSF) barriers. Transmigration of lymphocyte subsets across these barriers and their activation/differentiation within the periphery and intrathecal compartments in health and autoinflammatory CNS disease are complex. Mathematical models are warranted that qualitatively and quantitatively predict the distribution and differentiation stages of lymphocyte subsets in the blood and CSF. Here, we propose a probabilistic mathematical model that (i) correctly reproduces acquired data on location and differentiation states of distinct lymphocyte subsets under homeostatic and neuroinflammatory conditions, (ii) provides a quantitative assessment of differentiation and transmigration rates under these conditions, (iii) correctly predicts the qualitative behavior of immune-modulating therapies, (iv) and enables simulation-based prediction of distribution and differentiation stages of lymphocyte subsets in the case of limited access to biomaterial. Taken together, this model might reduce future measurements in the CSF compartment and allows for the assessment of the effectiveness of different immune-modulating therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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