Conference
Presentation_1_Omics-Based Approach Reveals Complement-Mediated Inflammation in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS).PDF
| العنوان: | Presentation_1_Omics-Based Approach Reveals Complement-Mediated Inflammation in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS).PDF |
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| المؤلفون: | Morten Blaabjerg, Anne Louise Hemdrup, Lylia Drici, Klemens Ruprecht, Peter Garred, Romana Höftberger, Bjarne W. Kristensen, Daniel Kondziella, Tobias Sejbaek, Soren W. Hansen, Helle H. Nielsen, Pia Jensen, Morten Meyer, Friedemann Paul, Hans Lassmann, Martin R. Larsen, Zsolt Illes |
| سنة النشر: | 2018 |
| المجموعة: | Frontiers: Figshare |
| مصطلحات موضوعية: | Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, CLIPPERS, proteomics, complement, cerebrospinal fluid, VCAM-1, ICAM-1, interleukin-8, multiple sclerosis |
| الوصف: | Objective Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF) by comprehensive methodologies. Materials and methods To identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome (n = 5) to a neurodegenerative condition, Alzheimer’s disease (AD, n = 5). Activation of complement was confirmed by immunohistochemistry (IHC) on CLIPPERS brain samples (n = 3) and by ELISA in the CSF. For potential biomarkers, we used biomarker arrays, and compared inflammatory and vessel-associated proteins in the CSF of CLIPPERS (n = 5) with another inflammatory relapsing CNS disease, multiple sclerosis (RMS, n = 9) and healthy subjects (HS, n = 7). Results Two hundred and seven proteins in the CSF discriminated CLIPPERS from AD. The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. Pathway analysis of upstream regulators suggested the importance of vascular cell adhesion protein 1 (VCAM1), IFN-γ, interleukin (IL)-1, and IL-10. Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. Besides endothelial cell damage, reactivity to smooth muscle actin was lost in the walls of inflamed vessels, but the glia limitans was preserved. The semi-quantitative array indicated that increased level of IL-8/CXCL8 (p < 0.05), eotaxin/CCL11 (p < 0.01), and granulocyte colony-stimulating factor (p < 0.05) in CSF could distinguish CLIPPERS from HS. The quantitative array confirmed ... |
| نوع الوثيقة: | conference object |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/presentation/Presentation_1_Omics-Based_Approach_Reveals_Complement-Mediated_Inflammation_in_Chronic_Lymphocytic_Inflammation_With_Pontine_Perivascular_Enhancement_Responsive_to_Steroids_CLIPPERS_PDF/6170765 |
| DOI: | 10.3389/fimmu.2018.00741.s001 |
| الاتاحة: | https://doi.org/10.3389/fimmu.2018.00741.s001 https://figshare.com/articles/presentation/Presentation_1_Omics-Based_Approach_Reveals_Complement-Mediated_Inflammation_in_Chronic_Lymphocytic_Inflammation_With_Pontine_Perivascular_Enhancement_Responsive_to_Steroids_CLIPPERS_PDF/6170765 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.93F5CB74 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2018.00741.s001 |
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