19 results on '"Vloet R"'
Search Results
2. Preliminary evaluation of a bunyavirus vector for cancer immunotherapy
- Author
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Oreshkova, N., Spel, L., Vloet, R. P M, Wichgers Schreur, P. J., Moormann, R. J M, Boes, M., Kortekaas, J., Oreshkova, N., Spel, L., Vloet, R. P M, Wichgers Schreur, P. J., Moormann, R. J M, Boes, M., and Kortekaas, J.
- Published
- 2015
3. Preliminary evaluation of a bunyavirus vector for cancer immunotherapy
- Author
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Immuno/reuma onderzoek 2 (Boes), Infection & Immunity, Child Health, CTI Nierkens, Oreshkova, N., Spel, L., Vloet, R. P M, Wichgers Schreur, P. J., Moormann, R. J M, Boes, M., Kortekaas, J., Immuno/reuma onderzoek 2 (Boes), Infection & Immunity, Child Health, CTI Nierkens, Oreshkova, N., Spel, L., Vloet, R. P M, Wichgers Schreur, P. J., Moormann, R. J M, Boes, M., and Kortekaas, J.
- Published
- 2015
4. Preliminary Evaluation of a Bunyavirus Vector for Cancer Immunotherapy
- Author
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Oreshkova, N., primary, Spel, L., additional, Vloet, R. P. M., additional, Wichgers Schreur, P. J., additional, Moormann, R. J. M., additional, Boes, M., additional, and Kortekaas, J., additional
- Published
- 2015
- Full Text
- View/download PDF
5. The FcRgamma chain is not essential for induction of experimental allergic encephalomyelitis (EAE) or anti-myelin antibody-mediated exacerbation of EAE
- Author
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Breij, Ecw, Heijnen, P., Vloet, R., Takashi Saito, Winkel, Jgj, Dijkstra, Cd, Amor, S., Verbeek, S., Molecular cell biology and Immunology, Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, and AII - Inflammatory diseases
- Abstract
Macrophages are considered essential mediators in multiple sclerosis (MS) pathogenesis, presumably through myelin phagocytosis and release of inflammatory mediators. Macrophages and microglia express activating Fcgamma receptors (FcgammaRI and FcgammaRIII), which depend on the FcRgamma chain for surface expression and signaling. In MS lesions, crosslinking of FcgammaR by immunoglobulins (IgG) directed against myelin may enhance myelin phagocytosis and inflammation. We studied the role of FcgammaR and anti-myelin antibodies in MOG35-55-induced experimental allergic encephalomyelitis (EAE) in C57BL/6 mice, a model of MS-like disease. Incidence and severity of EAE were similar in FcRy chain-/- (FcRgamma-/-) and wild-type (wt) mice, albeit with delayed onset in FcRgamma-/- mice. This demonstrates that the FcRy chain is not essential for induction of EAE, but that FcRgamma signaling may contribute to the preclinical phase. The role of FcgammaR in antibody-mediated demyelination was addressed by injection of anti-myelin antibodies (Z12 mAb) at onset of MOG35-55-induced EAE. Injection of Z12 mAb rapidly reduced survival time in both wt and FcRgamma-/- mice, demonstrating that antibody-mediated exacerbation of EAE is independent of the FcRgamma chain. Interestingly, Z12-induced exacerbation of inflammation and demyelination persisted longer in wt than FcRgamma-/- mice, suggesting that IgG-FcgammaR interactions may contribute to a sustained pathologic effect of anti-myelin antibodies in the CNS.
- Published
- 2005
6. European ring trial to evaluate ELISAs for the diagnosis of infection with Rift Valley fever virus
- Author
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Kortekaas, J., Kant, J., Vloet, R., Cêtre-Sossah, C., Marianneau, P., Lacote, S., Banyard, A. C., Jeffries, C., Eiden, M., Groschup, M. H., Jäckel, S., Hevia, E., Brun Torres, Alejandro, Kortekaas, J., Kant, J., Vloet, R., Cêtre-Sossah, C., Marianneau, P., Lacote, S., Banyard, A. C., Jeffries, C., Eiden, M., Groschup, M. H., Jäckel, S., Hevia, E., and Brun Torres, Alejandro
- Abstract
A ring trial was organized to evaluate Rift Valley fever virus (RVFV) ELISAs by European laboratories. A total of five ELISAs, two of which specific for IgM antibodies, were evaluated by six participants. Sera were derived from cattle or sheep and originated from either a RVFV endemic area, a RVFV-free area or from experimental infection studies. Cohen's kappa analysis showed higher than 90% agreement of two commercially available ELISAs with the virus neutralization test, suggesting that primary screening as well as serological confirmation using these ELISAs is feasible. More extensive validations with sera of known IgM status are, however, required to determine agreement between IgM ELISAs. © 2012 Elsevier B.V.
- Published
- 2013
7. Vertical Transmission of Rift Valley Fever Virus Without Detectable Maternal Viremia
- Author
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Antonis, A.F.G., primary, Kortekaas, J., additional, Kant, J., additional, Vloet, R. P. M., additional, Vogel-Brink, A., additional, Stockhofe, N., additional, and Moormann, R.J.M., additional
- Published
- 2013
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8. Molecular Characterization of Serratia marcescens Strain Isolated from Yellow Mealworms, Tenebrio molitor , in The Netherlands.
- Author
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Bello Gonzalez TDJ, van Gelderen B, Harders F, Vloet R, Voorbergen-Laarman M, de Ruiter B, and Haenen OLM
- Abstract
Insect culture has developed rapidly worldwide; it faces important security and safety control issues, including animal infections and disease development. In the Netherlands, in 2021, a ~30% mortality of mealworms, Tenebrio molitor , occurred at one farm, where over-humid sites in the substrate were observed. Bacterial cultures from both the external and internal partsof fry and larger mealworms were identified by MALDI-TOF to predominantly Serratia marcescens, Staphylococcus xylosus and Staphylococus saprofyticus . Due to the important role of S. marcescens as a potential zoonotic bacterium, we performed a molecular characterization of the isolated strain. Genomic analysis showed a multidrug-resistant S. marcescens isolate carrying a tet (41), aac (6')- Ic , and bla SST-1 chromosomal class C beta-lactamase-resistantgenes, all located on the chromosome. Additionally, several virulence genes were identified. The phylogenetic tree revealed that the S. marcescens strain from this study was similar to other S. marcescens strains from different ecological niches. Although the entomopathogenic activity was not confirmed, this case demonstrates that T. molitor can act as a reservoir and as an alternative path for exposing clinically important antibiotic-resistant bacteria that can affect animals and humans. It underlines the need to keep management factors optimal, before insects and their products enter the feed and food chain.
- Published
- 2023
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9. Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model.
- Author
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Gerhards NM, Cornelissen JBWJ, van Keulen LJM, Harders-Westerveen J, Vloet R, Smid B, Vastenhouw S, van Oort S, Hakze-van der Honing RW, Gonzales JL, Stockhofe-Zurwieden N, de Jong R, van der Poel WHM, Vreman S, Kortekaas J, Wichgers Schreur PJ, and Oreshkova N
- Abstract
In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment.
- Published
- 2021
- Full Text
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10. Reverse Genetics System for Shuni Virus, an Emerging Orthobunyavirus with Zoonotic Potential.
- Author
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Oymans J, Wichgers Schreur PJ, van Oort S, Vloet R, Venter M, Pijlman GP, van Oers MM, and Kortekaas J
- Subjects
- Animals, Bunyaviridae Infections transmission, Communicable Diseases, Emerging transmission, Genome, Viral, High-Throughput Nucleotide Sequencing, Mice, Open Reading Frames, Orthobunyavirus classification, Phylogeny, RNA, Viral, Rats, United Kingdom epidemiology, Viral Zoonoses transmission, Bunyaviridae Infections epidemiology, Bunyaviridae Infections virology, Communicable Diseases, Emerging epidemiology, Communicable Diseases, Emerging virology, Orthobunyavirus genetics, Reverse Genetics, Viral Zoonoses epidemiology, Viral Zoonoses virology
- Abstract
The genus Orthobunyavirus (family Peribunyaviridae , order Bunyavirales ) comprises over 170 named mosquito- and midge-borne viruses, several of which cause severe disease in animals or humans. Their three-segmented genomes enable reassortment with related viruses, which may result in novel viruses with altered host or tissue tropism and virulence. One such reassortant, Schmallenberg virus (SBV), emerged in north-western Europe in 2011. Shuni virus (SHUV) is an orthobunyavirus related to SBV that is associated with neurological disease in horses in southern Africa and recently caused an outbreak manifesting with neurological disease and birth defects among ruminants in Israel. The zoonotic potential of SHUV was recently underscored by its association with neurological disease in humans. We here report a reverse genetics system for SHUV and provide first evidence that the non-structural (NSs) protein of SHUV functions as an antagonist of host innate immune responses. We furthermore report the rescue of a reassortant containing the L and S segments of SBV and the M segment of SHUV. This novel reverse genetics system can now be used to study SHUV virulence and tropism, and to elucidate the molecular mechanisms that drive reassortment events.
- Published
- 2020
- Full Text
- View/download PDF
11. Vertical transmission of Rift Valley fever virus without detectable maternal viremia.
- Author
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Antonis AF, Kortekaas J, Kant J, Vloet RP, Vogel-Brink A, Stockhofe N, and Moormann RJ
- Subjects
- Animals, Antibodies, Viral blood, Female, Netherlands epidemiology, Pregnancy, Pregnancy Complications, Infectious mortality, Pregnancy Complications, Infectious virology, RNA, Viral analysis, Real-Time Polymerase Chain Reaction veterinary, Rift Valley Fever mortality, Rift Valley Fever virology, Rift Valley fever virus isolation & purification, Sheep, Sheep Diseases mortality, Sheep Diseases virology, Viremia veterinary, Infectious Disease Transmission, Vertical veterinary, Pregnancy Complications, Infectious veterinary, Rift Valley Fever transmission, Rift Valley fever virus physiology, Sheep Diseases transmission
- Abstract
Rift Valley fever virus (RVFV) is a zoonotic bunyavirus that causes abortions in domesticated ruminants. Sheep breeds exotic to endemic areas are reportedly the most susceptible to RVFV infection. Within the scope of a risk assessment program of The Netherlands, we investigated the susceptibility of a native breed of gestating sheep to RVFV infection. Ewes were infected experimentally during the first, second, or third trimester of gestation. Mortality was high among ewes that developed viremia. Four of 11 inoculated ewes, however, did not develop detectable viremia nor clinical signs and did not seroconvert for immunoglobulin G (IgG) or IgM antibodies. Surprisingly, these ewes were found to contain viral RNA in maternal and fetal organs, and the presence of live virus in fetal organs was demonstrated by virus isolation. We demonstrate that RVFV can be transmitted vertically in the absence of detectable maternal viremia.
- Published
- 2013
- Full Text
- View/download PDF
12. European ring trial to evaluate ELISAs for the diagnosis of infection with Rift Valley fever virus.
- Author
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Kortekaas J, Kant J, Vloet R, Cêtre-Sossah C, Marianneau P, Lacote S, Banyard AC, Jeffries C, Eiden M, Groschup M, Jäckel S, Hevia E, and Brun A
- Subjects
- Animals, Cattle, Cattle Diseases diagnosis, Cattle Diseases immunology, Europe, Neutralization Tests, Rift Valley Fever diagnosis, Rift Valley Fever immunology, Sensitivity and Specificity, Sheep, Sheep Diseases diagnosis, Sheep Diseases immunology, Antibodies, Viral blood, Enzyme-Linked Immunosorbent Assay veterinary, Immunoglobulin M blood, Rift Valley Fever veterinary, Rift Valley fever virus immunology
- Abstract
A ring trial was organized to evaluate Rift Valley fever virus (RVFV) ELISAs by European laboratories. A total of five ELISAs, two of which specific for IgM antibodies, were evaluated by six participants. Sera were derived from cattle or sheep and originated from either a RVFV endemic area, a RVFV-free area or from experimental infection studies. Cohen's kappa analysis showed higher than 90% agreement of two commercially available ELISAs with the virus neutralization test, suggesting that primary screening as well as serological confirmation using these ELISAs is feasible. More extensive validations with sera of known IgM status are, however, required to determine agreement between IgM ELISAs., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
13. Efficacy of three candidate Rift Valley fever vaccines in sheep.
- Author
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Kortekaas J, Antonis AF, Kant J, Vloet RP, Vogel A, Oreshkova N, de Boer SM, Bosch BJ, and Moormann RJ
- Subjects
- Adjuvants, Immunologic administration & dosage, Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Disease Models, Animal, Fever prevention & control, Rift Valley Fever immunology, Sheep, Survival Analysis, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic immunology, Viremia prevention & control, Rift Valley Fever prevention & control, Rift Valley fever virus immunology, Viral Vaccines administration & dosage, Viral Vaccines immunology
- Abstract
Rift Valley fever virus (RVFV) is a mosquito-transmitted Bunyavirus that causes high morbidity and mortality among ruminants and humans. The virus is endemic to the African continent and the Arabian Peninsula and continues to spread into new areas. The explosive nature of RVF outbreaks requires that vaccines provide swift protection after a single vaccination. We recently developed several candidate vaccines and here report their efficacy in lambs within three weeks after a single vaccination. The first vaccine comprises the purified ectodomain of the Gn structural glycoprotein formulated in a water-in-oil adjuvant. The second vaccine is based on a Newcastle disease virus-based vector that produces both RVFV structural glycoproteins Gn and Gc. The third vaccine comprises a recently developed nonspreading RVFV. The latter two vaccines were administered without adjuvant. The inactivated whole virus-based vaccine produced by Onderstepoort Biological Products was used as a positive control. Five out of six mock-vaccinated lambs developed high viremia and fever and one lamb succumbed to the challenge infection. A single vaccination with each vaccine resulted in a neutralizing antibody response within three weeks after vaccination and protected lambs from viremia, pyrexia and mortality., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
14. Protective efficacy of a Classical swine fever virus C-strain deletion mutant and ability to differentiate infected from vaccinated animals.
- Author
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Kortekaas J, Ketelaar J, Vloet RP, and Loeffen WL
- Subjects
- Animals, Antibodies, Viral blood, Classical Swine Fever physiopathology, Enzyme-Linked Immunosorbent Assay veterinary, Sequence Deletion, Swine, Vaccination, Vaccines, Attenuated immunology, Viral Envelope Proteins genetics, Classical Swine Fever immunology, Classical Swine Fever prevention & control, Classical Swine Fever Virus genetics, Classical Swine Fever Virus immunology, Viral Vaccines immunology
- Abstract
Classical swine fever (CSF) continues to be the most economically damaging pig disease in the world. The disease can be effectively controlled by vaccination with the live C-strain vaccine. This vaccine, however, does not enable the serological differentiation between infected and vaccinated animals (DIVA) and its use can therefore impose severe trade restrictions. CSF-specific diagnostic ELISAs detect antibodies directed against the conserved and immunodominant A domain of the E2 structural glycoprotein. We previously reported the production of a C-strain virus in which the immunodominant TAVSPTTLR epitope of the A domain is stably mutated with the aim to render the virus suitable as a DIVA vaccine. We here report that a single vaccination with this vaccine virus protected pigs from a lethal challenge dose of the highly virulent Brescia strain. Analysis of the sera, however, demonstrated that a commercially available E2 ELISA was unsuitable as an accompanying DIVA test., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
15. Rift Valley fever virus immunity provided by a paramyxovirus vaccine vector.
- Author
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Kortekaas J, de Boer SM, Kant J, Vloet RP, Antonis AF, and Moormann RJ
- Subjects
- Animals, Female, Mice, Mice, Inbred BALB C, Rift Valley Fever prevention & control, Rift Valley fever virus pathogenicity, Sheep, Newcastle disease virus immunology, Rift Valley Fever immunology, Rift Valley fever virus immunology, Viral Vaccines immunology
- Abstract
Rift Valley fever virus (RVFV) causes recurrent large outbreaks among humans and livestock. Although the virus is currently confined to the African continent and the Arabian Peninsula, there is a growing concern for RVFV incursions into countries with immunologically naïve populations. The RVFV structural glycoproteins Gn and Gc are preferred targets in the development of subunit vaccines that can be used to control future outbreaks. We here report the production of Gn and Gc by a recombinant vaccine strain of the avian paramyxovirus Newcastle disease virus (NDV) and demonstrate that intramuscular vaccination with this experimental NDV-based vector vaccine provides complete protection in mice. We also demonstrate that a single intramuscular vaccination of lambs, the main target species of RVFV, is sufficient to elicit a neutralizing antibody response.
- Published
- 2010
- Full Text
- View/download PDF
16. Intramuscular inoculation of calves with an experimental Newcastle disease virus-based vector vaccine elicits neutralizing antibodies against Rift Valley fever virus.
- Author
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Kortekaas J, Dekker A, de Boer SM, Weerdmeester K, Vloet RP, de Wit AA, Peeters BP, and Moormann RJ
- Subjects
- Administration, Intranasal, Animals, Cattle, Injections, Intramuscular, Rift Valley fever virus genetics, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, Viral Vaccines administration & dosage, Viral Vaccines genetics, Antibodies, Neutralizing blood, Antibodies, Viral blood, Genetic Vectors, Newcastle disease virus genetics, Rift Valley fever virus immunology, Viral Vaccines immunology
- Abstract
In the past decade, the use of Newcastle disease virus (NDV) as a vaccine vector for the prevention of economically important livestock diseases as well as for human diseases has been extensively explored. In this study, we have constructed a recombinant NDV vaccine virus, named NDFL-Gn, that produces the Rift Valley fever virus (RVFV) Gn glycoprotein. Calves were immunized via either the intranasal route or the intramuscular route. Delivery via the intranasal route elicited no detectable antibody responses, whereas delivery via the intramuscular route elicited antibodies against both NDV and the Gn protein. The RVFV-neutralizing activity of the antisera from intramuscularly vaccinated calves was demonstrated, suggesting that NDV is a promising vaccine vector for the prevention of RVF in calves., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
17. Rational design of a classical swine fever C-strain vaccine virus that enables the differentiation between infected and vaccinated animals.
- Author
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Kortekaas J, Vloet RP, Weerdmeester K, Ketelaar J, van Eijk M, and Loeffen WL
- Subjects
- Animals, Classical Swine Fever Virus genetics, Epitopes genetics, Epitopes immunology, Evolution, Molecular, Models, Biological, Mutation, Missense immunology, Rabbits, Sequence Deletion immunology, Vaccines, Attenuated genetics, Vaccines, Attenuated immunology, Viral Envelope Proteins genetics, Viral Envelope Proteins immunology, Virus Replication, Antibodies, Viral blood, Classical Swine Fever immunology, Classical Swine Fever Virus immunology, Viral Vaccines immunology
- Abstract
The C-strain of the classical swine fever virus (CSFV) is considered the gold standard vaccine for the control of CSF. This vaccine, however, does not enable the serological differentiation between infected and vaccinated animals (DIVA). Consequently, its use can impose severe trade restrictions. The immunodominant and evolutionarily conserved A-domain of the E2 structural glycoprotein is an important target in CSFV-specific ELISAs. With the ultimate aim to render the C-strain suitable as a DIVA vaccine, mutations were introduced that were expected to dampen the immunogenicity of the A-domain. In the first of two approaches, the feasibility of shielding the A-domain by N-linked glycans was evaluated, whereas in the second approach C-strain mutants were created with targeted deletions in the A-domain. Analysis of the antibody responses elicited in rabbits suggested that shielding of the A-domain by an N-linked glycan had a minor effect on the immune response against the A-domain, whereas a targeted deletion of only a single amino acid severely dampened this response. C-strain mutants with larger deletions were highly debilitated and incapable of sustained growth in vitro. By providing the viruses with the opportunity to increase their fitness by mutation, a mutant was rescued that found a way to compensate for the imposed fitness cost. Most of the identified mutations occurred in several independently evolved viruses, demonstrating parallel evolution. By virtue of this compensatory evolution, a well replicating and genetically stable C-strain mutant was produced that can be serologically differentiated from wildtype CSFV. The findings provide the molecular basis for the development of a novel, genetically stable, live attenuated CSF DIVA vaccine., (2009 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
18. Homogeneity of active demyelinating lesions in established multiple sclerosis.
- Author
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Breij EC, Brink BP, Veerhuis R, van den Berg C, Vloet R, Yan R, Dijkstra CD, van der Valk P, and Bö L
- Subjects
- Adult, Aged, Apoptosis immunology, Autoantibodies analysis, Autoantibodies immunology, Autoantigens immunology, Autoimmunity immunology, Autopsy, Biomarkers analysis, Biomarkers metabolism, Central Nervous System immunology, Central Nervous System metabolism, Complement Activation immunology, Complement System Proteins analysis, Complement System Proteins immunology, Disease Progression, Female, Humans, Immunoglobulin G analysis, Immunoglobulin G immunology, Macrophages immunology, Macrophages pathology, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis immunology, Multiple Sclerosis metabolism, Myelin-Associated Glycoprotein analysis, Myelin-Associated Glycoprotein immunology, Oligodendroglia immunology, Oligodendroglia pathology, Central Nervous System pathology, Multiple Sclerosis pathology, Nerve Fibers, Myelinated pathology
- Abstract
Objective: Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS., Methods: All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging-guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions., Results: Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found., Interpretation: The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fcgamma receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS.
- Published
- 2008
- Full Text
- View/download PDF
19. The FcRgamma chain is not essential for induction of experimental allergic encephalomyelitis (EAE) or anti-myelin antibody-mediated exacerbation of EAE.
- Author
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Breij EC, Heijnen P, Vloet R, Saito T, van de Winkel JG, Dijkstra CD, Amor S, and Verbeek S
- Subjects
- Animals, Demyelinating Diseases immunology, Inflammation immunology, Macrophages immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Myelin Proteins, Myelin-Associated Glycoprotein immunology, Myelin-Oligodendrocyte Glycoprotein, Protein Subunits genetics, Receptors, IgG genetics, Survival Rate, Antibodies, Monoclonal immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Myelin Sheath immunology, Protein Subunits metabolism, Receptors, IgG metabolism
- Abstract
Macrophages are considered essential mediators in multiple sclerosis (MS) pathogenesis, presumably through myelin phagocytosis and release of inflammatory mediators. Macrophages and microglia express activating Fcgamma receptors (FcgammaRI and FcgammaRIII), which depend on the FcRgamma chain for surface expression and signaling. In MS lesions, crosslinking of FcgammaR by immunoglobulins (IgG) directed against myelin may enhance myelin phagocytosis and inflammation. We studied the role of FcgammaR and anti-myelin antibodies in MOG35-55-induced experimental allergic encephalomyelitis (EAE) in C57BL/6 mice, a model of MS-like disease. Incidence and severity of EAE were similar in FcRy chain-/- (FcRgamma-/-) and wild-type (wt) mice, albeit with delayed onset in FcRgamma-/- mice. This demonstrates that the FcRy chain is not essential for induction of EAE, but that FcRgamma signaling may contribute to the preclinical phase. The role of FcgammaR in antibody-mediated demyelination was addressed by injection of anti-myelin antibodies (Z12 mAb) at onset of MOG35-55-induced EAE. Injection of Z12 mAb rapidly reduced survival time in both wt and FcRgamma-/- mice, demonstrating that antibody-mediated exacerbation of EAE is independent of the FcRgamma chain. Interestingly, Z12-induced exacerbation of inflammation and demyelination persisted longer in wt than FcRgamma-/- mice, suggesting that IgG-FcgammaR interactions may contribute to a sustained pathologic effect of anti-myelin antibodies in the CNS.
- Published
- 2005
- Full Text
- View/download PDF
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