Reich und schön mit Informationskompetenz

Informationskompetenz (IK) ist in aller Munde, auch in Konstanz. In diesem Artikel wollen wir klären, welche Rolle die Vermittlung von IK in Konstanz spielt und spielen wird, und welche Aktivitäten und Projekte dazu bereits vor Ort existieren

Xenogeneic Neu5Gc and self-glycan Neu5Ac epitopes are potential immune targets in MS.

OBJECTIVE To explore the repertoire of glycan-specific immunoglobulin G (IgG) antibodies in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS). METHODS A systems-level approach combined with glycan array technologies was used to determine specificities and binding reactivities of glycan-specific IgGs in treatment-naive patients with RRMS compared with patients with noninflammatory and other inflammatory neurologic diseases. RESULTS We identified a unique signature of glycan-binding IgG in MS with high reactivities to the dietary xenoglycan N-glycolylneuraminic acid (Neu5Gc) and the self-glycan N-acetylneuraminic acid (Neu5Ac). Increased reactivities of serum IgG toward Neu5Gc and Neu5Ac were additionally observed in an independent, treatment-naive cohort of patients with RRMS. CONCLUSION Patients with MS show increased IgG reactivities to structurally related xenogeneic and human neuraminic acids. The discovery of these glycan-specific epitopes as immune targets and potential biomarkers in MS merits further investigation

Dağlar çocuğu

C. C.'nin Talebe Defteri'nde tefrika edilen Dağlar Çocuğu adlı roman

Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5

Intrathecal IgM production in multiple sclerosis (MS) is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in MS, CSF from two independent cohorts, including MS patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS- related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of MS donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced and used to produce recombinant monoclonal antibodies for characterisation and antigen identification. We produced 5 cell-binding recombinant IgM antibodies, of which one, cloned from an HLA-DR + plasma-like B cell, mediated antigen-dependent complement activation. Immunoprecipitation and mass spectrometry, and biochemical and transcriptome analysis of the target cells identified the iron transport scavenger protein SCARA5 as the antigen target of this antibody. Intrathecal injection of a SCARA5 antibody led to an increased T cell infiltration in an EAE model. CSF IgM might contribute to CNS inflammation in MS by binding to cell surface antigens like SCARA5 and activating complement, or by facilitating immune cell migration into the brain

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection

Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands

BackgroundInclusion of cerebrospinal fluid (CSF) oligoclonal IgG bands (OCGB) in the revised McDonald criteria increases the sensitivity of diagnosis when dissemination in time (DIT) cannot be proven. While OCGB negative patients are unlikely to develop clinically definite (CD) MS, OCGB positivity may lead to an erroneous diagnosis in conditions that present similarly, such as neuromyelitis optica spectrum disorders (NMOSD) or neurosarcoidosis.ObjectiveTo identify specific, OCGB-complementary, biomarkers to improve diagnostic accuracy in OCGB positive patients.MethodsWe analysed the CSF metabolome and proteome of CDMS (n=41) and confirmed non-MS patients (n=64) comprising a range of CNS conditions routinely encountered in neurology clinics.ResultsOCGB discriminated between CDMS and non-MS with high sensitivity (85%), but low specificity (67%), as previously described. Machine learning methods revealed CCN5 levels provide greater accuracy, sensitivity, and specificity than OCGB (79%, +5%; 90%, +5%; and 72%, +5% respectively) while glial fibrillary acidic protein (GFAP) identified CDMS with 100% specificity (+33%). A multiomics approach improved accuracy further to 90% (+16%).ConclusionThe measurement of a few additional CSF biomarkers could be used to complement OCGB and improve the specificity of MS diagnosis when clinical and radiological evidence of DIT is absent

Complement Activation Is Associated With Disease Severity in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES Histopathologic studies have identified immunoglobulin (Ig) deposition and complement activation as contributors of CNS tissue damage in multiple sclerosis (MS). Intrathecal IgM synthesis is associated with higher MS disease activity and severity, and IgM is the strongest complement-activating immunoglobulin. In this study, we investigated whether complement components (CCs) and complement activation products (CAPs) are increased in persons with MS, especially in those with an intrathecal IgM synthesis, and whether they are associated with disease severity and progression. METHODS CC and CAP levels were quantified in plasma and CSF of 112 patients with clinically isolated syndrome (CIS), 127 patients with MS (90 relapsing-remitting, 14 primary progressive, and 23 secondary progressive), 31 inflammatory neurologic disease, and 44 symptomatic controls from the Basel CSF databank study. Patients with CIS/MS were followed in the Swiss MS cohort study (median 6.3 years). Levels of CC/CAP between diagnosis groups were compared; in CIS/MS, associations of CC/CAP levels with intrathecal Ig synthesis, baseline Expanded Disability Status Scale (EDSS) scores, MS Severity Score (MSSS), and neurofilament light chain (NfL) levels were investigated by linear regression, adjusted for age, sex, and albumin quotient. RESULTS CSF (but not plasma) levels of C3a, C4a, Ba, and Bb were increased in patients with CIS/MS, being most pronounced in those with an additional intrathecal IgM production. In CIS, doubling of C3a and C4a in CSF was associated with 0.31 (CI 0.06-0.56; p = 0.016) and 0.32 (0.02-0.62; p = 0.041) increased EDSS scores at lumbar puncture. Similarly, doubling of C3a and Ba in CIS/MS was associated with 0.61 (0.19-1.03; p < 0.01) and 0.74 (0.18-1.31; p = 0.016) increased future MSSS. In CIS/MS, CSF levels of C3a, C4a, Ba, and Bb were associated with increased CSF NfL levels, e.g., doubling of C3a was associated with an increase of 58% (Est. 1.58; CI 1.37-1.81; p < 0.0001). DISCUSSION CNS-compartmentalized activation of the classical and alternative pathways of complement is increased in CIS/MS and associated with the presence of an intrathecal IgM production. Increased complement activation within the CSF correlates with EDSS, future MSSS, and NfL levels, supporting the concept that complement activation contributes to MS pathology and disease progression. Complement inhibition should be explored as therapeutic target to attenuate disease severity and progression in MS

Untersuchung eines endovaskulären Ansatzes zur Therapie zerebraler Aneurysmen auf der Basis magnetischer Mikropartikel : tierexperimentelle und In-vitro Untersuchungen

OBJECTIVE: Endovascular treatment of intracranial aneurysms employing endosaccular coiling can be associated with aneurysm perforation, coil herniation or incomplete obliteration fueling the interest to investigate novel endovascular techniques. We aimed to test a novel embolization material in experimental aneurysms in vitro and in vivo whereby intra-arterially administered magnetic microparticles (MMPs) are navigated into the lumen of vascular aneurysms with assistance from an external magnetic field.METHODS: MMPs are core-shell particles suspended in saline that have a shell made of a polymeric material and a core made of magnetite (Fe3O4). They have a diameter of 1.4 mm. During MMP administration via a microcatheter, a magnetic field was applied externally to direct the particles with the use of a solid-state neodymium magnet. Experiments were performed in a perfused silicone vessel and aneurysm model to evaluate application techniques and fluid dynamics and in the elastase aneurysm model in rabbits to evaluate in vivo compatibility, including multiorgan histological examinations and long-term stability of aneurysm embolization.RESULTS: It was possible to steer and hold the MMPs within the aneurismal cavity where they occluded the lumen progressively. After removal of the external magnetic field, the results remained stable in vivo for the remainder of the observational period (30 minutes); after a 12-week observational period, recanalization of the aneurysm occured.CONCLUSION: MMPs can be magnetically directed into aneurysms, allowing short-term obliteration. Although the method has yet to show reliable long-term stability, these experiments provide proof of concept, encouraging further investigation of intravascular magnetic compounds