scholarly journals No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 845
Author(s):  
An Hotterbeekx ◽  
Melissa Krizia Vieri ◽  
Melanie Ramberger ◽  
Ashraf Jozefzoon-Aghai ◽  
Michel Mandro ◽  
...  
Keyword(s):  
Rat Brain ◽  
Autoimmune Disorder ◽  
Acute Onset ◽  
Post Mortem ◽  
Serum Samples ◽  
Specific Staining ◽  
Nodding Syndrome ◽  
Post Mortem Brain ◽  
A Cell ◽  
Capillary Walls

Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.

scholarly journals Hepcidin Increases Cytokines in Alzheimer’s Disease and Down’s Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation

2021 ◽  
Vol 13 ◽  
Author(s):  
Animesh Alexander Raha ◽  
Seyedeh Deniz Ghaffari ◽  
James Henderson ◽  
Subhojit Chakraborty ◽  
Kieren Allinson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Iron Homeostasis ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Post Mortem ◽  
Serum Samples ◽  
Iron Storage ◽  
Post Mortem Brain ◽  
Serum Hepcidin

The liver-derived hormone hepcidin, a member of the defensin family of antimicrobial peptides, plays an important role in host defense and innate immunity due to its broad antibacterial and antiviral properties. Ferritin, an iron storage protein is often associated with iron deficiency, hypoferritinemia, hypoxia, and immune complications, which are all significant concerns for systemic infection in Alzheimer’s disease (AD) and Down’s syndrome (DS) dementia. Serum and post-mortem brain samples were collected from AD, DS and age-matched control subjects. Serum samples were analyzed with ELISA for ferritin, hepcidin and IL-6. Additionally, post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins. A significant increase in serum hepcidin levels was found in DS, compared to controls and AD subjects (p < 0.0001). Hepcidin protein was visible in the epithelial cells of choroid plexus, meningeal macrophages and in the astrocytes close to the endothelium of blood vessels. Hepcidin co-localized with IL-6, indicating its anti-inflammatory properties. We found significant correlation between hypoferritinemia and elevated levels of serum hepcidin in AD and DS. Hepcidin can be transported via macrophages and the majority of the vesicular hepcidin enters the brain via a compromised blood brain barrier (BBB). Our findings provide further insight into the molecular implications of the altered iron metabolism in acute inflammation, and can aid towards the development of preventive strategies and novel treatments in the fight against neuroinflammation.

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

scholarly journals PEDV Infection Generates Conformation-Specific Antibodies That Can Be Effectively Detected by a Cell-Based ELISA

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 303
Author(s):  
Wei-Ting Hsu ◽  
Chia-Yu Chang ◽  
Chih-Hsuan Tsai ◽  
Sung-Chan Wei ◽  
Huei-Ru Lo ◽  
...  
Keyword(s):  
Recombinant Baculovirus ◽  
Immunocytochemical Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Perfect Agreement ◽  
Specific Antibodies ◽  
Diarrhea Virus ◽  
Serological Studies ◽  
A Cell ◽  
Infected Insect

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes serious and highly contagious enteric disease in swine worldwide. In this study, we constructed a recombinant baculovirus (S-Bac) expressing full-length spike protein of the virulent epidemic genotype 2b (G2b) PEDV strain for serological studies of infected pigs. We found that most spike-specific antibodies produced upon PEDV infection in pigs are conformation-specific and they could be detected on S-Bac-infected insect cells by immunofluorescent assay, but they were insensitive to Western blot analysis, the typical method for antiserum analysis. These results indicated that spike conformation is crucial for serum recognition. Since it is difficult to purify trimeric spike membrane protein for conventional enzyme-linked immunosorbent assay (ELISA), we used S-Bac to generate a novel cell-based ELISA for convenient PEDV detection. We analyzed 100 pig serum samples, and our cell-based ELISA exhibited a sensitivity of 100%, a specificity of 97%, and almost perfect agreement [Cohen’s kappa coefficient value (κ) = 0.98] with immunocytochemical staining results. Our cell-based ELISA rapidly presented antigen for proper detection of conformation-specific antibodies, making PEDV detection more convenient, and it will be useful for detecting many viral diseases in the future.

scholarly journals Serum Metabolomic Profiles of Rheumatoid Arthritis Patients With Acute-Onset Diffuse Interstitial Lung Disease

2019 ◽  
Vol 14 ◽  
pp. 117727191987047 ◽  
Author(s):  
Hiroshi Furukawa ◽  
Shomi Oka ◽  
Kota Shimada ◽  
Atsushi Hashimoto ◽  
Akiko Komiya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Stable State ◽  
Area Under The Curve ◽  
Stable Condition ◽  
Hierarchical Cluster ◽  
Acute Onset ◽  
Serum Samples ◽  
Drug Induced

Objective: Acute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and Pneumocystis pneumonia, and frequently occurs in patients with rheumatoid arthritis (RA). Since AoDILD causes a poor prognosis in RA, biomarkers for AoDILD were eagerly desired. Metabolomic analyses were extensively performed in cancer patients and successfully generated better diagnostic biomarkers. In the present study, serum metabolomic profiles of AoDILD in RA were investigated to generate better potential metabolomic biomarkers. Methods: Serum samples of 10 RA patients with AoDILD were collected on admission and in a stable state, more than 3 months before the admission. Serum metabolomic analyses were conducted on the samples from these RA patients with AoDILD. Results: Apparently distinct serum metabolomic profiles in AoDILD were not observed in univariate or hierarchical cluster analyses. Partial least squares-discriminant analysis (PLS-DA) was performed to select candidate metabolites based on variable importance in projection (VIP) scores. The PLS-DA model generated from the four metabolites with VIP scores more than 2.25 (mannosamine, alliin, kynurenine, and 2-hydroxybutyric acid) could successfully discriminate AoDILD from the stable condition (area under the curve: 0.962, 95% confidence interval: 0.778–1.000). Conclusion: It was demonstrated that metabolomic profiling was useful to generate better biomarkers in AoDILD.

P1-155: Post-Mortem Brain Tissue Characterisation of Inflammatory and Pathological Hallmarks of Alzheimer’s Disease During Disease Progression

2016 ◽  
Vol 12 ◽  
pp. P462-P462
Author(s):  
Martina M. Hughes ◽  
Beatriz G. Perez-Nievas ◽  
Claire Troakes ◽  
Michael Perkinton ◽  
Diane P. Hanger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Brain Tissue ◽  
Post Mortem ◽  
Tissue Characterisation ◽  
Post Mortem Brain

scholarly journals Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain

2015 ◽  
Vol 28 (1) ◽  
pp. 18-31 ◽  
Author(s):  
Jeremy Duncan ◽  
Niping Wang ◽  
Xiao Zhang ◽  
Shakevia Johnson ◽  
Sharonda Harris ◽  
...  
Keyword(s):  
Cell Death ◽  
Rat Brain ◽  
Social Stress ◽  
Chronic Social Stress ◽  
A Cell

scholarly journals Cerebellar peduncle abscess secondary to disseminated strangles in a six-week-old miniature foal

2011 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Brianne Henderson
Keyword(s):  
Animal Health ◽  
Clinical Signs ◽  
Acute Onset ◽  
Abscess Formation ◽  
Neurological Deficits ◽  
Post Mortem ◽  
Streptococcus Equi ◽  
The Central Nervous System ◽  
Cerebellar Peduncle ◽  
The Right

During a strangles outbreak within a herd of minature horses, a six week old foal developed acute onset clinical signs of sepsis and neurological deficits. The foal was euthanized and submitted for post-mortem at the Animal Health Laboratories, Guelph Ontario. Gross <em>post-mortem</em> examination noted severe bronchopneumonia, hypopyon of the right eye and a singular cerebellar peduncle abscess. Culture of the lungs and cerebellum produced a pure growth of <em>Streptococcus equi</em> ssp. <em>equi</em>. <em>Streptococcus equi</em> ssp. <em>equi</em>, the causative agent of equine strangles, produces an acute pyrexia, purulent lymphadenopathy of submandibular and retropharyngeal lymph nodes. Commonly, lymph node abscesses rupture and resolve without complication. Rarely, complications may include: dissemination of the bacteria with diffuse abscess formation, immune mediated disease (purpura haemorrhagica), rarely abscess formation within the central nervous system (CNS) can occur. These can be managed medically with appropriate antibiotics and drugs to reduce intra-cranial pressure, however surgical drainage and debulking of the abscess has been attempted successfully in a few cases.

scholarly journals The choice of embedding media affects image quality, tissue R 2 * , and susceptibility behaviors in post‐mortem brain MR microscopy at 7.0T

2018 ◽  
Vol 81 (4) ◽  
pp. 2688-2701 ◽  
Author(s):  
Petr Dusek ◽  
Vince Istvan Madai ◽  
Till Huelnhagen ◽  
Erik Bahn ◽  
Radoslav Matej ◽  
...  
Keyword(s):  
Image Quality ◽  
Post Mortem ◽  
Mr Microscopy ◽  
Post Mortem Brain
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