About: Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects
Creator	Bielekova, Bibiana Kosa, Peter Romm, Elena Stein, Jason Wu, Tianxia Xu, Quangang Gran, Bruno Gross, Catharina Jackson, Kayla Kc, Jackson Tackenberg, Björn Wuest, Simone
Source	PMC
abstract	Although B cell depletion is an effective therapy of multiple sclerosis (MS), the pathogenic functions of B cells in MS remain incompletely understood. We asked whether cerebrospinal fluid (CSF) B cells in MS secrete different cytokines than control-subject B cells and whether cytokine secretion affects MS phenotype. We blindly studied CSF B cells after their immortalization by Epstein-Barr Virus (EBV) in prospectively-collected MS patients and control subjects with other inflammatory-(OIND) or non-inflammatory neurological diseases (NIND) and healthy volunteers (HV). The pilot cohort (n = 80) was analyzed using intracellular cytokine staining (n = 101 B cell lines [BCL] derived from 35 out of 80 subjects). We validated differences in cytokine production in newly-generated CSF BCL (n = 207 BCL derived from subsequent 112 prospectively-recruited subjects representing validation cohort), using ELISA enhanced by objective, flow-cytometry-based B cell counting. After unblinding the pilot cohort, the immortalization efficiency was almost 5 times higher in MS patients compared to controls (p < 0.001). MS subjects' BCLs produced significantly more vascular endothelial growth factor (VEGF) compared to control BCLs. Progressive MS patients BCLs produced significantly more tumor necrosis factor (TNF)-α and lymphotoxin (LT)-α than BCL from relapsing-remitting MS (RRMS) patients. In the validation cohort, we observed lower secretion of IL-1β in RRMS patients, compared to all other diagnostic categories. The validation cohort validated enhanced VEGF-C production by BCL from RRMS patients and higher TNF-α and LT-α secretion by BCL from progressive MS. No significant differences among diagnostic categories were observed in secretion of IL-6 or GM-CSF. However, B cell secretion of IL-1β, TNF-α, and GM-CSF correlated significantly with the rate of accumulation of disability measured by MS disease severity scale (MS-DSS). Finally, all three cytokines with increased secretion in different stages of MS (i.e., VEGF-C, TNF-α, and LT-α) enhance lymphangiogenesis, suggesting that intrathecal B cells directly facilitate the formation of tertiary lymphoid follicles, thus compartmentalizing inflammation to the central nervous system.
has issue date	2018-07-20(xsd:dateTime)
bibo:doi	10.3389/fneur.2018.00554
bibo:pmid	30079049
has license	cc-by
sha1sum (hex)	b9c267b7dcc9a8348248c04a8bf604aa52926101
schema:url	https://doi.org/10.3389/fneur.2018.00554
resource representing a document's title	Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects
has PubMed Central identifier	PMC6062589
has PubMed identifier	30079049
schema:publication	Front Neurol
resource representing a document's body	covid:b9c267b7dcc9a8348248c04a8bf604aa52926101#body_text
is schema:about of	named entity 'SUBJECTS' named entity 'VASCULAR ENDOTHELIAL GROWTH FACTOR' named entity 'EPSTEIN-BARR VIRUS' named entity 'OBSERVED' named entity 'B CELLS' named entity 'ENHANCED' named entity '28P' named entity 'PATIENTS' named entity 'GENERATED' named entity 'B CELL DEPLETION' named entity 'HIGHER' named entity 'DSS' named entity 'SIGNIFICANT' named entity 'USING' named entity 'SUBJECTS' named entity 'FUNCTIONS' named entity 'MEASURED' named entity 'MULTIPLE SCLEROSIS' named entity 'VALIDATED' named entity 'LOWER' named entity 'UNDERSTOOD' named entity 'VALIDATION' named entity '101' named entity 'DERIVED' named entity 'DISABILITY' named entity 'CSF' named entity 'SEVERITY SCALE' named entity 'INTRACELLULAR CYTOKINE STAINING' named entity 'FLOW' named entity 'RATE' named entity 'CEREBROSPINAL FLUID' named entity 'PHENOTYPE' named entity 'PILOT' named entity 'RELAPSING-REMITTING MS' named entity 'DIAGNOSTIC' named entity 'GM-CSF' named entity 'PROGRESSIVE MS' named entity 'PATHOGENIC' named entity 'SUBSEQUENT' named entity 'IMMORTALIZATION' named entity 'VEGF-C' named entity 'TIMES' named entity 'UNBLINDING' named entity 'CYTOMETRY' named entity 'DISEASES' named entity 'TO CONTROL' named entity 'BASED' named entity 'NEWLY' named entity 'TUMOR NECROSIS FACTOR ' named entity 'NEUROLOGICAL' named entity 'ACCUMULATION' named entity 'RRMS' named entity 'BCL' named entity 'COMPARED' named entity 'DERIVED' named entity 'POTENTIAL' named entity 'CORRELATED' named entity 'MS.' named entity 'NONINFLAMMATORY' covid:arg/b9c267b7dcc9a8348248c04a8bf604aa52926101 named entity 'STEIN' named entity 'HAVE' named entity 'NON-' named entity 'GREATER' named entity 'B CELLS' named entity 'CYTOKINE PRODUCTION' named entity 'CELL LINES' named entity 'COMPARED' named entity 'SECRETE' named entity 'EFFICIENCY'

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