High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica

BackgroundNeuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood.PurposeTo detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value.MethodsWe obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA.ResultsSerum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores.ConclusionsOur results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.

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Glycan Shedding in both the Blood and CSF: Initial Predictor of Immune Attack in Autoimmune Encephalomyelitis?

10.21203/rs.2.22182/v1 ◽

2020 ◽

Author(s):

Shanshan Pei ◽

Jiajia Zhu ◽

Zheyi Zhou ◽

Yuewen Ding ◽

Yu Peng ◽

...

Keyword(s):

Neurological Diseases ◽

Clinical Situation ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Autoimmune Encephalomyelitis ◽

Holistic Understanding ◽

Luminal Side ◽

Diagnostic Role ◽

Csf Levels

Abstract Background Neuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy belong to autoimmune diseases incentral nervous system mainly manifestate encephalomyelitis. The glycocalyx (GLX), consists of several membrane-bound macromolecules, is located on the luminal side of the endothelium and mediates the blood and the vessel interaction. Until now, there is still lacking a holistic understanding of the GLX degradation in autoimmune encephalomyelitis. Aim This study aimed to detect the shedding levels of GLX components, heparan sulfate (HS) and hyaluronic acid (HA) in serum and cerebrospinal fluid (CSF), correlate them with the severity and assess the diagnostic value of them, and evaluate their correlations with pro-inflammatory cytokines. Methods Serum and CSF samples were obtained from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS, HA and IFN-γ, IL-17A, matrix metalloproteinase (MMP)-1 were detected by enzyme linked immunosorbent assay ELISA. Results Besides levels of serum and CSF levels of HS, HA and related cytokines were significantly elevated in these diseases. Notably, HS, HA in NMO, MS patients, and autoimmune GFAP astrocytopathy diseases were widely correlated with EDSS scores. Importantly, the ROC curve analysis suggested a potential diagnostic role of HS or HA . Conclusions The results here suggested the GLX degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate worse clinical situation. Importantly, CSF HS and HA may be informative diagnostic biomarkers for telling autoimmune encephalomyelitis from the non-inflammatory neurological controls. Furthermore, therapeutic strategy for protecting GLX may be effective to these diseases.

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Serum Immunoglobulin G level and Neutrophils to Lymphocytes Ratio Associated with the Prognosis of Neuromyelitis Optica Spectrum Disorder

Current Neurovascular Research ◽

10.2174/1567202618666210702113526 ◽

2021 ◽

Vol 18 ◽

Author(s):

Ying Tong ◽

Li Wang ◽

Kai Liu ◽

Weishi Liu ◽

Shen Li ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Neuromyelitis Optica ◽

Immunoglobulin G ◽

Peripheral Blood ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Positive Group ◽

Serum Igg ◽

High Level ◽

Igg Level

Objective: To investigate the factors related to the prognosis of neuromyelitis optica spectrum disorder (NMOSD) in cerebrospinal fluid and peripheral blood examination. Methods: In this study, we collected 111 patients who were admitted to the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2018 and diagnosed with NMOSD. The patients were divided into the relapse group (n=48) and remission group (n=67). Before treatment, all the patients underwent a routine cerebrospinal fluid (CSF) and peripheral blood test on the second morning of admission. The association between laboratory data and disease prognosis was evaluated. Results: The immunoglobulin G (IgG) level in the serum showed a strong correlation with the relapse of patients, especially in the aquaporin-4-Antibody (AQP4-Ab) positive group (p<0.01). A high level of serum IgG concentration was associated with the relapse of NMOSD, especially in the anti-AQP4 positive group. The area under the receiver operating characteristic (ROC) curve of serum IgG level was 0.888 (p0.001, 95%CI: 0.808-0.968). The ratio of neutrophils to lymphocytes (NLR) was associated with the disability degree of NMOSD patients in 3 years. The NLR value was a linear correlation with final Expanded Disability Status Scale (EDSS) scores. Patients with a high level of NLR value presented an increased degree of disability in the following three years (R2=0.053, p=0.015). Conclusion: The serum IgG level and NLR of first-attack patients were correlated with the prognosis of NMOSD.

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Interleukin-6 and granulocyte macrophage-csf in the cerebrospinal fluid from hiv infected subjects with involvement of the central nervous system

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1992000200008 ◽

1992 ◽

Vol 50 (2) ◽

pp. 180-182 ◽

Cited By ~ 18

Author(s):

O. Perrella ◽

M. Guerriero ◽

E. Izzo ◽

M. Soscia ◽

P. B. Carrieri

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Interleukin 6 ◽

Neurological Diseases ◽

Aids Dementia Complex ◽

Gm Csf ◽

Aids Dementia ◽

High Incidence ◽

The Central Nervous System ◽

Csf Levels

We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM-CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC.

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Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510392619 ◽

2010 ◽

Vol 17 (5) ◽

pp. 521-531 ◽

Cited By ~ 47

Author(s):

Jorge Correale ◽

Marcela Fiol

Keyword(s):

Multiple Sclerosis ◽

Neuromyelitis Optica ◽

Immune Cell ◽

Neurological Diseases ◽

Relapsing Remitting ◽

Inflammatory Processes ◽

Csf Levels ◽

Immune Cell Response ◽

In Vitro Bbb Model

Background: Recent studies conducted in arthritis, asthma, and inflammatory bowel disease suggest that chitinases are important in inflammatory processes and tissue remodeling. Objective: To investigate the role of chitinases in multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods: Levels of chitotriosidase, acid mammalian chitinase (AMCase), and chitinase 3-like-1 (CHI3L1) were measured using ELISA, in cerebrospinal fluid (CSF) and in serum from 24 patients with relapsing remitting (RR) MS, 24 patients with secondary progressive (SP) MS, 12 patients with NMO, 24 patients with other inflammatory neurological diseases (OIND), and 24 healthy controls (HCs). The number of anti-MOG cytokine-secreting cells was studied using ELISPOT. Eotaxins, MCP-1, RANTES, and IL-8 were assessed using ELISA. Cell transmigration was determined using an in vitro blood–brain barrier (BBB) model, in the presence and absence of chitinases. Results: CSF chitinase levels were significantly increased in patients with RRMS and NMO compared with HCs and patients with SPMS and OIND. In contrast, no significant differences were detected in serum chitinase levels between groups. Chitinase CSF levels showed correlation with anti-MOG IL-13-producing cells, and eotaxin levels. In vitro experiments showed macrophage chitinase secretion was significantly increased by IL-13, but not by IL-5, IL-6, IL-12, or IFN-γ. Moreover, chitinases enhanced IL-8, RANTES, MCP-1, and eotaxin production, increasing migratory capacity in eosinophils, T cells, and macrophages across an in vitro BBB model. Conclusions: Chitinases increased in the CSF from patients with NMO in response to IL-13. These enhanced levels could contribute to central nervous system inflammation by increasing immune cell migration across the BBB.

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CSF-S100B Is a Potential Candidate Biomarker for Neuromyelitis Optica Spectrum Disorders

BioMed Research International ◽

10.1155/2018/5381239 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Yuzhen Wei ◽

Haoxiao Chang ◽

Xindi Li ◽

Li Du ◽

Wangshu Xu ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Neurological Diseases ◽

Potential Candidate ◽

Expanded Disability Status Scale ◽

Pathologic Feature ◽

Disability Status ◽

Csf Levels ◽

Spectrum Disorders ◽

Wbc Count ◽

Aquaporin 4 Antibody

Astrocytic impairment is a pathologic feature of neuromyelitis optica spectrum disorder (NMOSD). S100B and glial fibrillary acidic protein (GFAP) are the two most commonly used astrocytic markers. The aim of this study was to evaluate whether CSF-S100B could serve as a marker of NMOSD. We enrolled 49 NMOSD patients [25 aquaporin-4 antibody (AQP4-Ab)–positive, 8 myelin-oligodendrocyte glycoprotein antibody (MOG-Ab)-positive, and 16 seronegative patients], 12 multiple sclerosis (MS) patients, and 15 other noninflammatory neurological diseases (OND) patients. The CSF levels of S100B and GFAP were measured by ELISA. Both CSF-S100B and GFAP levels significantly discriminated NMOSD from MS [area under curve (AUC) = 0.839 and 0.850, respectively] and OND (AUC = 0.839 and 0.850, respectively). The CSF-S100B levels differentiated AQP4-Ab–positive NMOSD from MOG-Ab–positive NMOSD with higher accuracy than the CSF-GFAP levels (AUC=0.865 and 0.772, respectively). The CSF-S100B levels also significantly discriminated MOG-Ab–positive patients from seronegative patients (AUC = 0.848). Both CSF-S100B and GFAP levels were correlated with the Expanded Disability Status Scale (EDSS) during remission. Only the CSF-S100B levels were correlated with the CSF WBC count and the EDSS during attack. The levels of CSF-S100B seemed to have a longer lasting time than the levels of CSF-GFAP, which may benefit patients who present late. As a result, CSF-S100B might be a potential candidate biomarker for NMOSD in discriminating, evaluating severity, and predicting disability.

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High Level of Soluble CD146 In Cerebrospinal Fluid Might be a Biomarker of Severity of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.680424 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qing Li ◽

Jinglong Chen ◽

Mengzhuo Yin ◽

Jun Zhao ◽

Fuchang Lu ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Neurological Diseases ◽

Neurological Status ◽

Acute Stage ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

Potential Biomarker ◽

Tnf Α ◽

Multi Center Study ◽

High Level

BackgroundDisruption of the blood–brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis.MethodTwenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge.ResultssCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls.ConclusionOur data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

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Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease

BioMed Research International ◽

10.1155/2020/3812671 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Wurong Li ◽

Wenqing Wu ◽

Haoxiao Chang ◽

Meijuan Jiang ◽

Junhua Gao ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Microglial Activation ◽

Neuronal Injury ◽

Interleukin 10 ◽

Diagnostic Value ◽

Neurofilament Light ◽

Penicillin Therapy ◽

Csf Levels ◽

Wbc Count ◽

Necrosis Factor

The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1β, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) α; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients (p<0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients (p=0.024 and p<0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.

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Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

Sexually Transmitted Infections ◽

10.1136/sextrans-2018-053813 ◽

2019 ◽

Vol 95 (4) ◽

pp. 246-250 ◽

Cited By ~ 7

Author(s):

Huan Chen ◽

Yuan Zhou ◽

Zhao-Yuan Wang ◽

Bing-Xi Yan ◽

Wei-Fang Zhou ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Real Time Pcr ◽

Statistical Difference ◽

Neurological Diseases ◽

Quantitative Real Time Pcr ◽

Mirna Array ◽

Csf Levels ◽

First Time ◽

Exosomal Microrna ◽

Potential Biomarkers

ObjectiveChanges in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF of patients suffering from neurosyphilis.MethodsExosomes were isolated from serum and CSF. Levels of 44 miRNAs were determined using quantitative real-time PCR-based miRNA array.ResultsIn patients with neurosyphilis (NSP), miR-590-5p, miR-570-3p and miR-570-5p were upregulated in the CSF and serum, when compared with patients with syphilis without neurosyphilis (SP). miR-590-5p and miR-570-3p were significantly upregulated (p<0.001). The expression of miR-21-5p was upregulated only in the CSF of NSP. Significant downregulation was observed for miR-93-3p in the CSF and serum of NSP. No statistical difference was found in the expression of miR-7-5p, miR-1307-5p, miR-203a-3p, miR-16, miR-23b-3p and miR-27b-5p in the CSF and serum of NSP and SP.ConclusionFor the first time, regulation profiles in miRNA in the CSF and serum were analysed in NSP. We found significant differences in upregulation and downregulation. Therefore, miRNAs may be potential biomarkers for the presence of neurosyphilis.

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Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100015663 ◽

2012 ◽

Vol 39 (6) ◽

pp. 813-820 ◽

Cited By ~ 19

Author(s):

Aimin Wu ◽

Xiaonan Zhong ◽

Honghao Wang ◽

Wen Xu ◽

Chen Cheng ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Neuromyelitis Optica ◽

Demyelinating Diseases ◽

Enzyme Linked Immunosorbent Assay ◽

Human Central Nervous System ◽

Immune Activity ◽

Humoral Immune ◽

Csf Concentration

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown.Object:To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity.Methods:CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).Results:CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027).Conclusions:The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

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Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis

Disease Markers ◽

10.1155/2017/2467870 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Zhen Zhang ◽

Chenglin Tian ◽

Qiang Shi ◽

Jing Hao ◽

Na Zhao ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Diagnostic Accuracy ◽

Neurological Diseases ◽

Leptomeningeal Metastasis ◽

Serum Levels ◽

Diagnostic Value ◽

Receiver Operating Curve ◽

Cytokeratin 19 ◽

Paired Samples ◽

Significant Difference

Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits.

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