scholarly journals Multi-proteomic Analysis Revealed Distinct Protein Profiles in Cerebrospinal Fluid of Patients Between Anti-NMDAR Encephalitis NORSE and Cryptogenic NORSE

2021 ◽  
Author(s):  
Dongmei Wang ◽  
Yongming Wu ◽  
Yue Pan ◽  
Shengnan Wang ◽  
Guanghui Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Cerebrospinal Fluid ◽  
Clinical Features ◽  
Cell Apoptosis ◽  
Proteomic Analysis ◽  
Inflammatory Cytokine ◽  
Protein Microarray ◽  
Regulation Of Transcription ◽  
Nmdar Encephalitis ◽  
Cytokine Array

Abstract Background: New-onset refractory status epilepticus (NORSE) caused by anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis and cryptogenic etiologies are various in clinical features. The underlying mechanisms of the diseases have still remained elusive.Methods: 6 patients with anti-NMDAR encephalitis NORSE, 5 with cryptogenic NORSE (C-NORSE), and 5 controls were enrolled. Clinical data, including clinical features, cerebrospinal fluid (CSF) samples, and cranial images were collected. CSF samples were tested for FAIMS based quantitative proteomic analysis, immunome protein microarray, and inflammatory cytokine array. Bioinformatics and immunostaining were used for interpretation and verification.Results: The clinical features of anti-NMDAR encephalitis NORSE and C-NORSE patients were similar to those reported previously. Proteomic analysis revealed that 101 proteins (63 up-regulated and 38 down-regulated) and 56 proteins (42 up-regulated and 14 down-regulated) changed in CSF samples of anti-NMDAR encephalitis NORSE and C-NORSE patients, respectively. The mean fold-change of the up-regulated proteins, namely up-proteomic score in this study, was positively associated with the severity of disease, including ICU stay, mRS score at discharge, and time taken for patients awaking from a coma. The distribution of changed proteins in CSF between the two diseases were quite different. Pathways of humoral immune response, wound healing, and epigenetic regulation of transcription were up-regulated in anti-NMDAR encephalitis NORSE. Pathways of innate and lymphocyte mediated immune response, synaptic functions, ubiquitination, and cell apoptosis were up-regulated in C-NORSE group, suggesting that C-NORSE could undergo neurodegeneration. This was consistent with a mouse model of SE, which showed high ubiquitination and cell apoptosis in CA1 to CA3 regions of hippocampus. Immunome microarray analysis demonstrated high autoantibody targeting 48 proteins in CSF samples of anti-NMDAR encephalitis NORSE. However, in C-NORSE, the reaction was kept at a very low level. Inflammatory cytokine array, unexpectedly, showed no remarkable changes except for decreased level of interleukin-6 (IL-6) in both anti-NMDAR encephalitis NORSE and C-NORSE.Conclusions: The present study suggests that the up-proteomic score of CSF could be a promising indicator for assessment of the severity of anti-NMDAR encephalitis NORSE and C-NORSE. The distinct CSF proteomes imply different pathogenic mechanisms of the two diseases, and immunotherapy strategies as well.

scholarly journals Acetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis

2019 ◽  
Vol 317 (5) ◽  
pp. G557-G568 ◽  
Author(s):  
Rose A. Willemze ◽  
David J. Brinkman ◽  
Olaf Welting ◽  
Patricia H. P. van Hamersveld ◽  
Caroline Verseijden ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Cytokine ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Innate Immune ◽  
Cytokine Levels ◽  
Colitis Model

Clinical trials suggest that vagus nerve stimulation presents an alternative approach to classical immune suppression in Crohn's disease. T cells capable of producing acetylcholine (ChAT+ T cells) in the spleen are essential mediators of the anti-inflammatory effect of vagus nerve stimulation. Besides the spleen, ChAT+ T cells are found abundantly in Peyer’s patches of the small intestine. However, the role of ChAT+ T cells in colitis pathogenesis is unknown. Here, we made use of CD4creChATfl/fl mice (CD4ChAT−/− mice) lacking ChAT expression specifically in CD4+ T cells. Littermates (ChATfl/fl mice) served as controls. In acute dextran sulfate sodium (DSS)-induced colitis (7 days of 2% DSS in drinking water), CD4ChAT−/− mice showed attenuated colitis and lower intestinal inflammatory cytokine levels compared with ChATfl/fl mice. In contrast, in a resolution model of DSS-induced colitis (5 days of 2% DSS followed by 7 days without DSS), CD4ChAT−/− mice demonstrated a worsened colitis recovery and augmented colonic histological inflammation scores and inflammatory cytokine levels as compared with ChATfl/fl mice. In a transfer colitis model using CD4+CD45RBhigh T cells, T cells from CD4ChAT−/− mice induced a similar level of colitis compared with ChATfl/fl T cells. Together, our results indicate that ChAT+ T cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, whereas they are supporting the later resolution process of this innate immune-driven colitis. Surprisingly, ChAT expression in T cells seems redundant in the context of T cell-driven colitis. NEW & NOTEWORTHY By using different mouse models of experimental colitis, we provide evidence that in dextran sulfate sodium-induced colitis, ChAT+ T cells capable of producing acetylcholine worsen the acute immune response, whereas they support the later healing phase of this innate immune-driven colitis.

Sex-Related Differences in Rat Choroid Plexus and Cerebrospinal Fluid: A cDNA Microarray and Proteomic Analysis

2016 ◽  
Vol 28 (1) ◽  
Author(s):  
T. Quintela ◽  
H. Marcelino ◽  
M. J. Deery ◽  
R. Feret ◽  
J. Howard ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Cdna Microarray ◽  
Proteomic Analysis

scholarly journals Identification of the Feline Humoral Immune Response to Bartonella henselae Infection by Protein Microarray

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11447 ◽  
Author(s):  
Adam Vigil ◽  
Rocio Ortega ◽  
Aarti Jain ◽  
Rie Nakajima-Sasaki ◽  
Xiaolin Tan ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Bartonella Henselae ◽  
Protein Microarray ◽  
Humoral Immune

scholarly journals A Proteomic Analysis of Individual and Gender Variations in Normal Human Urine and Cerebrospinal Fluid Using iTRAQ Quantification

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133270 ◽  
Author(s):  
Zhengguang Guo ◽  
Yang Zhang ◽  
Lili Zou ◽  
Danqi Wang ◽  
Chen Shao ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Human Urine ◽  
Proteomic Analysis ◽  
Normal Human ◽  
And Gender ◽  
Gender Variations

Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

2018 ◽  
Vol 49 (16) ◽  
pp. 2709-2716 ◽  
Author(s):  
Ronald J. Gurrera
Keyword(s):  
Nmda Receptor ◽  
Clinical Features ◽  
Psychiatric Symptoms ◽  
Autoimmune Encephalitis ◽  
Signs And Symptoms ◽  
Nmda Receptor Encephalitis ◽  
Nmdar Encephalitis ◽  
Unexplained Fever ◽  
Study Inclusion

AbstractBackgroundAnti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.MethodsA systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.ResultsTwo hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.ConclusionsClinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

scholarly journals Identification of Tumor-Related Proteins by Proteomic Analysis of Cerebrospinal Fluid from Patients with Primary Brain Tumors

2003 ◽  
Vol 62 (8) ◽  
pp. 855-862 ◽  
Author(s):  
Ping-Pin Zheng ◽  
Theo M. Luider ◽  
Rob Pieters ◽  
Cees J.J. Avezaat ◽  
Martin J. van den Bent ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Proteomic Analysis ◽  
Primary Brain Tumors ◽  
Related Proteins

scholarly journals The influence of sepsis as a complication after trauma on immune response to injury

2011 ◽  
Vol 139 (3-4) ◽  
pp. 179-184
Author(s):  
Maja Surbatovic ◽  
Darko Mirkovic ◽  
Sonja Radakovic ◽  
Miodrag Jevtic ◽  
Nikola Filipovic
Keyword(s):  
Immune Response ◽  
Mortality Rate ◽  
Inflammatory Response ◽  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Elisa Test ◽  
Sepsis Group ◽  
Blood Samples ◽  
Significant Difference ◽  
Anti Inflammatory Cytokine

Introduction. Mortality rate in trauma complicated with sepsis is exceeding 50%. Outcome is not determined only by infection or trauma, but also by the intensity of immuno-inflammatory response. Objective. The aim of this study was to determine the influence of sepsis on the immuno-inflammatory response, in the group of 35 traumatized men, of which in 25 cases trauma was complicated with sepsis. Methods. Cytokines were measured by ELISA test in plasma. Blood samples were drown on the first, third and fifth day after ICU admission. Results. Proinflammatory cytokine IL-8 was 230-fold higher in trauma + sepsis group (1148.48 vs. 5.05 pg/ml; p<0.01), and anti- inflammatory cytokine IL-1ra was 4-fold higher (1138.3 vs. 310.05 pg/ml; p<0.01), whereas IL-12 and IL-4 showed no significant difference between the groups. Conclusion. We concluded that sepsis, as a complication after trauma, drastically enhances immuno-inflammatory response to insult, as indicated by IL-8 and IL-1ra, but not IL-12 and IL-4.

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