Dataset Information

Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases.

ABSTRACT: The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case-control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.

SUBMITTER: Molero-Luis M

PROVIDER: S-EPMC7588460 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases.

Molero-Luis Marta M Casas-Alba Didac D Orellana Gabriela G Ormazabal Aida A Sierra Cristina C Oliva Clara C Valls Anna A Velasco Jesus J Launes Cristian C Cuadras Daniel D Pérez-Dueñas Belén B Jordan Iolanda I Cambra Francisco J FJ Ortigoza-Escobar Juan D JD Muñoz-Almagro Carmen C Garcia-Cazorla Angels A Armangué Thais T Artuch Rafael R

Scientific reports 20201026 1

The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case-control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified in ...[more]

PMID: 33106568

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Project description:A highly efficient recognition unit based on surface-enhanced Raman spectroscopy (SERS) was developed as a promising, fast, and sensitive tool for detection of meningococcal meningitis, which is an extremely serious and often fatal disease of the nervous system (an inflammation of the lining around the brain and spinal cord). The results of this study confirmed that there were specific differences in SERS spectra between cerebrospinal fluid (CSF) samples infected by Neisseria meningitidis and the normal CSF, suggesting a potential role for neopterin in meningococcal meningitis detection and screening applications. To estimate the best performance of neopterin as a marker of bacterial infection, principal component analysis (PCA) was performed in a selected region (640-720 cm(-1)) where the most prominent SERS peak at 695 cm(-1) arising from neopterin was observed. The calculated specificity of 95 % and sensitivity of 98 % clearly indicate the effective diagnostic efficiency for differentiation between infected and control samples. Additionally, the limit of detection (LOD) of neopterin in CSF clinical samples was estimated. The level of neopterin was significantly higher in CSF samples infected by N. meningitidis (48 nmol/L), compared to the normal (control) group (4.3 nmol/L). Additionally, this work presents a new type of SERS-active nanostructure, based on polymer mats, that allows simultaneous filtration, immobilization, and enhancement of the Raman signal, enabling detection of spectra from single bacterial cells of N. meningitidis present in CSF samples. This provides a new possibility for fast and easy detection of bacteria in CSF and other clinical body fluids on a time scale of seconds. This method of detection produces consistent results faster and cheaper than traditional laboratory techniques, demonstrates the powerful potential of SERS for detection of disease, and shows the viability of future development in healthcare applications.

Project description:In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Dataset Information

Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases.

Publications

Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases.

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