Dataset Information

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

ABSTRACT:

Background

Rapid and accurate diagnosis of central nervous system (CNS) infections is important, and laboratory tests help diagnose CNS infections. Even when the patient has symptoms, laboratory tests often do not reveal any specific findings. The potential of vitamin D-binding protein (VDBP) to be used as a biomarker for viral and bacterial CNS infections was studied.

Methods

A total of 302 subjects with suspected CNS infection who underwent lumbar puncture were included. Clinical and laboratory data were collected retrospectively. VDBP levels were measured in the cerebrospinal fluid (CSF) samples. Genotyping for the GC gene encoding VDBP was also performed. VDBP levels were analyzed and compared by CNS infection, pathogen, CSF opening pressure, and GC genotype.

Results

A CNS infection group (n?=?90) and a non-CNS infection group (n?=?212) were studied. In terms of its receiver operating characteristic, CSF VDBP showed an area under the curve of 0.726 for the diagnosis of CNS infection. CSF VDBP levels were significantly different between the CNS infection and non-infection groups. The CNS infection group with enterovirus showed a statistically lower distribution of CSF VDBP levels than the other virus groups. The group with CSF opening pressure > 25 cmH₂O showed higher CSF VDBP levels than the other groups. There was no significant difference in GC gene allele distribution between the CNS infection and non-infection groups.

Conclusions

CSF VDBP levels were increased in patients with CNS infection. The CSF VDBP showed potential as a new biomarker for viral and bacterial CNS infections.

SUBMITTER: Kim YJ

PROVIDER: S-EPMC7934275 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

Kim Young Jin YJ Lê Hương Giang HG Na Byoung-Kuk BK Kim Bo Gyu BG Jung Youn-Kwan YK Kim Mutbyul M Kang Heeyoung H Cho Min-Chul MC

BMC infectious diseases 20210305 1

<h4>Background</h4>Rapid and accurate diagnosis of central nervous system (CNS) infections is important, and laboratory tests help diagnose CNS infections. Even when the patient has symptoms, laboratory tests often do not reveal any specific findings. The potential of vitamin D-binding protein (VDBP) to be used as a biomarker for viral and bacterial CNS infections was studied.<h4>Methods</h4>A total of 302 subjects with suspected CNS infection who underwent lumbar puncture were included. Clinica ...[more]

PMID: 33673834

Similar Datasets

Project description:BackgroundDistinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique.MethodsIn this study, we extracted cell-free DNA from the CSF (CSF-cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet-digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease.ResultsBlood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF-cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF-cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18-93 days).ConclusionsThese results suggest that mutation analysis using CSF-cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.

Project description:The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-? peptide of 42 amino acids (A?1-42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST(®), Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The A?1-42/P-tau181P ratio (AUC?=?0.770) performed significantly better than A?1-42 (AUC?=?0.677, P?=?0.004), T-tau (AUC?=?0.592, P?<?0.001), and A?1-42/T-tau (AUC?=?0.678, P?=?0.001), while P-tau181P (AUC?=?0.720) performed significantly better than T-tau (AUC?=?0.592, P?<?0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, A?1-42/P-tau181P (AUC?=?0.894) discriminated AD from frontotemporal dementia significantly better than A?1-42 (AUC?=?0.776, P?=?0.020) and T-tau (AUC?=?0.746, P?=?0.004), while P-tau181P/T-tau (AUC?=?0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to A?1-42 (AUC?=?0.688, P?=?0.004), T-tau (AUC?=?0.874, P?=?0.040), and A?1-42/P-tau181P (AUC?=?0.760, P?=?0.003). In conclusion, this study demonstrates P-tau181P is an essential component of the AD CSF biomarker panel, and combined assessment of A?1-42, T-tau, and P-tau181P renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.

Project description:Differential diagnosis of bacterial meningitis (BM) and viral meningitis (VM) is a critical clinical challenge, as the early and accurate identification of the causative agent determines the appropriate treatment regimen and markedly improves patient outcomes. Clinical and experimental studies have demonstrated that the pathogen and the host immune response contribute to mortality and neurological sequelae. As BM is associated with the activation of an inflammatory cascade, the patterns of pro- and anti-inflammatory cytokines/chemokines (CTs/CKs) present in the cerebrospinal fluid (CSF) in response to the immune assault may be useful as sensitive markers for differentiating BM from VM. In the present study, the ability of CTs/CKs in the CSF to differentiate between BM and VM was investigated. For this, biochemical markers and CT/CK profiles were analysed in 145 CSF samples, divided into three groups: BM (n=61), VM (n=58) and the control group (C; n=26) comprising patients with meningism. The CSF concentrations of monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1β, IL-6, macrophage inflammatory protein-1α (MIP-1α), epithelial-neutrophil activating peptide, IL-10, tumour necrosis factor-α (TNF-α), proteins and white blood cells were significantly higher and the CSF glucose level was significantly lower in the BM group compared with the VM and C groups (P<0.01). Correlation analysis identified 28 significant correlations between various CTs/CKs in the BM group (P<0.01), with the strongest positive correlations being for TNF-α/IL-6 (r=0.75), TNF-α/MIP-1α (r=0.69), TNF-α/IL-1β (r=0.64) and IL-1β/MIP-1α (r=0.64). To identify the optimum CT/CK patterns for predicting and classifying BM and VM, a dataset of 119 BM and VM samples was divided into training (n=90) and testing (n=29) subsets for use as input for a Random Forest (RF) machine learning algorithm. For the 29 test samples (15 BM and 14 VM), the RF algorithm correctly classified 28 samples, with 92% sensitivity and 93% specificity. The results show that the patterns of CT/CK levels in the CSF can be used to aid discrimination of BM and VM.

Dataset Information

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

Background

Methods

Results

Conclusions

Publications

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets