In this consensus statement, we provide updated recommendations on multiple sclerosis (MS) management during the COVID-19 crisis and the post-pandemic period applicable to neurology services around the world. Statements/recommendations were generated based on available literature and the experience of 13 MS expert panelists using a modified Delphi approach online. The statements/recommendations give advice regarding implementation of telemedicine; use of disease-modifying therapies and management of MS relapses; management of people with MS at highest risk from COVID-19; management of radiological monitoring; use of remote pharmacovigilance; impact on MS research; implications for lowest income settings, and other key issues.
- Klíčová slova
- COVID-19, Disease-modifying treatment, Multiple sclerosis, Pharmacovigilance, Telemedicine,
- MeSH
- COVID-19 epidemiologie terapie MeSH
- farmakovigilance MeSH
- internacionalita * MeSH
- lidé MeSH
- management nemoci MeSH
- pandemie prevence a kontrola MeSH
- roztroušená skleróza epidemiologie terapie MeSH
- směrnice pro lékařskou praxi jako téma normy MeSH
- telemedicína normy trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- přehledy MeSH
Morphine- and Concanavalin A-induced changes of protein composition of rat spleen lymphocytes were determined by high-resolution proteomic analysis, gel-free, label-free quantification, MaxLFQ. Stimulation by Con A resulted in a major reorganization of spleen cell protein composition evidenced by increased expression level of 94 proteins; 101 proteins were down-regulated (>2-fold). Interestingly, among proteins that were up-regulated to the largest extent were the prototypical brain proteins as a neuron specific enolase, synapsin-1, brain acid-soluble protein-1 and myelin basic protein. Morphine-induced change was limited to no more than 5 up-regulated and 18 down-regulated proteins (>2-fold).
- Klíčová slova
- Concanavalin A, Morphine, Proteomic analysis, Rat spleen lymphocytes, Up-regulation of brain proteins,
- MeSH
- aktivace lymfocytů účinky léků genetika MeSH
- konkanavalin A farmakologie MeSH
- krysa rodu Rattus MeSH
- lymfocyty účinky léků metabolismus MeSH
- morfin farmakologie MeSH
- potkani Wistar MeSH
- proteom účinky léků MeSH
- proteomika metody MeSH
- regulace genové exprese účinky léků MeSH
- slezina cytologie MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- konkanavalin A MeSH
- morfin MeSH
- proteom MeSH
Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.
- Klíčová slova
- Anti-drug antibodies, Bridging ELISA, Interferon-beta, Luciferase-based bioassay, Multiple sclerosis, Neutralizing antibodies,
- MeSH
- biotest MeSH
- ELISA MeSH
- imunologické faktory imunologie terapeutické užití MeSH
- interferon beta imunologie terapeutické užití MeSH
- lidé MeSH
- neutralizační testy metody MeSH
- neutralizující protilátky krev MeSH
- roztroušená skleróza krev farmakoterapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- imunologické faktory MeSH
- interferon beta MeSH
- neutralizující protilátky MeSH
The presence of pre-existing natural antibodies against Alzheimer's disease (AD) pathological proteins might interfere with immune responses to therapeutic vaccination with these proteins. We aimed to compare levels of antibodies in CSF and serum: We observed higher reactivity of natural tau-reactive antibodies towards phosphorylated bovine tau protein than to human recombinant (non-phosphorylated) tau protein. Males with MCI-AD had higher amounts of these antibodies than corresponding controls. Concentrations of antibodies were lower in females with the MCI-AD than in control females. These findings may have implications for tau vaccination trials.
- Klíčová slova
- Alzheimer's disease, Antibody, Mild cognitive impairment, Post-translational modification, Sex, Tau protein,
- MeSH
- Alzheimerova nemoc krev mozkomíšní mok imunologie MeSH
- autoprotilátky analýza krev mozkomíšní mok MeSH
- demence krev mozkomíšní mok imunologie MeSH
- druhová specificita MeSH
- fosfoproteiny chemie imunologie MeSH
- fosforylace MeSH
- kognitivní dysfunkce krev mozkomíšní mok imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pohlavní dimorfismus * MeSH
- posttranslační úpravy proteinů MeSH
- proteiny tau chemie imunologie MeSH
- rekombinantní proteiny imunologie MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- skot MeSH
- specificita protilátek MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- autoprotilátky MeSH
- fosfoproteiny MeSH
- MAPT protein, human MeSH Prohlížeč
- proteiny tau MeSH
- rekombinantní proteiny MeSH
Regulation of μ-, δ- and κ-opioid receptor protein level in spleen lymphocytes when stimulated by mitogen is not known. To answer the question whether these cells do express opioid receptor (OR) proteins, primary, fresh rat spleen lymphocytes were prepared and stimulated for 48 h with mitogenic dose of Con A. The unstimulated lymphocytes did not express μ- and δ-OR proteins in detectable amounts, however, stimulation with Con A resulted in appearance of clearly detectable immunoblot signals of both μ-OR and δ-OR. κ-OR were detected already in primary cells and increased 2.4-fold in Con A-stimulated cells. These results were supported by data obtained by flow cytometry analysis indicating a dramatic increase in number of μ-, δ- and κ-OR expressing cells after mitogen stimulation. The newly synthesized μ-, δ- and κ-OR in Con A-stimulated spleen lymphocytes were present in the cells interior and not functionally mature, at least in terms of their ability to enhance activity of trimeric G proteins determined by three different protocols of agonist-stimulated, high-affinity [35S]GTPγS binding assay. The up-regulation of μ-, δ- and κ-OR was associated with specific decrease of their cognate trimeric G proteins, Gi1α/Gi2α; the other Gα and Gβ subunits were unchanged. The level of β-arrestin-1/2 was also decreased in Con A-stimulated splenocytes. We conclude that up-regulation of OR expression level in spleen lymphocytes by Con A proceeds in conjunction with down-regulation of their intracellular signaling partners, Gi1α/Gi2α proteins and β-arrestin-1/2. These regulatory proteins are expressed in high amounts already in unstimulated cells and decreased by mitogen stimulation.
- Klíčová slova
- Concanavalin A, G proteins, Opioids receptors, Rat spleen lymphocytes, Up-regulation, β-arrestin-1/2,
- MeSH
- konkanavalin A farmakologie MeSH
- krysa rodu Rattus MeSH
- lymfocyty účinky léků metabolismus MeSH
- mitogeny farmakologie MeSH
- potkani Wistar MeSH
- receptory opiátové delta biosyntéza účinky léků MeSH
- receptory opiátové kappa biosyntéza účinky léků MeSH
- receptory opiátové mu biosyntéza účinky léků MeSH
- slezina cytologie účinky léků metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- konkanavalin A MeSH
- mitogeny MeSH
- receptory opiátové delta MeSH
- receptory opiátové kappa MeSH
- receptory opiátové mu MeSH
Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab.
- Klíčová slova
- Alemtuzumab, CD4+ lymphocytes, Immune reconstitution, Multiple sclerosis, Treatment response,
- MeSH
- alemtuzumab terapeutické užití MeSH
- CD4-pozitivní T-lymfocyty účinky léků patologie MeSH
- dospělí MeSH
- lidé MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- roztroušená skleróza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alemtuzumab MeSH
- protinádorové látky imunologicky aktivní MeSH
The presence of natural tau-reactive antibodies was reported in human blood. In this study, we isolated and characterized natural tau-reactive antibodies occurring in IVIG product Flebogamma, plasma of patients with Alzheimer's disease (AD) and older cognitively normal persons (controls). Using blotting immunoassays and ELISA, we showed reactivity of antibodies obtained from IVIG and controls against a recombinant fragment of tau (155-421aa) and aggregates present in brains of AD patients. In contrast, antibodies isolated from plasma of AD patients reacted mainly with the recombinant full-length tau form and tau monomeric forms in brain tissue.
- Klíčová slova
- Alzheimer's disease, Brain homogenates, Plasma antibodies, Reactivity profile, Tau protein,
- MeSH
- Alzheimerova nemoc krev imunologie patologie terapie MeSH
- fosforylace MeSH
- imunoglobulin G krev klasifikace MeSH
- intravenózní imunoglobuliny krev imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek metabolismus MeSH
- proteiny tau imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobulin G MeSH
- intravenózní imunoglobuliny MeSH
- proteiny tau MeSH
Studies on Huntington's disease (HD) demonstrated altered immune response in HD gene carriers. Using multiplexing immunoassay, we simultaneously investigated seven cytokines in secretomes of microglia and blood monocytes, cerebrospinal fluid (CSF) and serum collected from transgenic HD minipigs at pre-symptomatic disease stage. Decline in IFNα and IL-10 was observed in CSF and secretome of microglia whilst elevated IL-8 and IL-1β levels were secreted by microglia. Additionally, IL-8 was increased in serum. The proportion of mutant huntingtin in microglia may have causative impact on cytokine production. IFNα, IL-10, IL-8 and IL-1β represent promising biomarkers reflecting immuno-pathological mechanisms in porcine HD model.
- Klíčová slova
- Biomarker(s), Central nervous system, Cytokines, Immune response, Porcine Huntington's disease model, Serum,
- MeSH
- biologické markery metabolismus MeSH
- centrální nervový systém cytologie patologie MeSH
- cytokiny metabolismus MeSH
- DNA vazebné proteiny metabolismus MeSH
- geneticky modifikovaná zvířata MeSH
- Huntingtonova nemoc genetika metabolismus patologie MeSH
- interferon alfa metabolismus MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- interleukin-8 metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- mikrofilamentové proteiny MeSH
- mikroglie účinky léků metabolismus MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- monocyty účinky léků metabolismus MeSH
- prasata MeSH
- protein huntingtin MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- proteiny vázající vápník MeSH
- regulace genové exprese genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AIF1 protein, human MeSH Prohlížeč
- biologické markery MeSH
- cytokiny MeSH
- DNA vazebné proteiny MeSH
- HTT protein, human MeSH Prohlížeč
- interferon alfa MeSH
- interleukin-10 MeSH
- interleukin-1beta MeSH
- interleukin-8 MeSH
- lipopolysacharidy MeSH
- mikrofilamentové proteiny MeSH
- protein huntingtin MeSH
- proteiny nervové tkáně MeSH
- proteiny vázající vápník MeSH
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction of skeletal muscles. Triple-seronegative MG (tSN-MG, without detectable AChR, MuSK and LRP4 antibodies), which accounts for ~10% of MG patients, presents a serious gap in MG diagnosis and complicates differential diagnosis of similar disorders. Several AChR antibody positive patients (AChR-MG) also have antibodies against titin, usually detected by ELISA. We have developed a very sensitive radioimmunoprecipitation assay (RIPA) for titin antibodies, by which many previously negative samples were found positive, including several from tSN-MG patients. The validity of the RIPA results was confirmed by western blots. Using this RIPA we screened 667 MG sera from 13 countries; as expected, AChR-MG patients had the highest frequency of titin antibodies (40.9%), while MuSK-MG and LRP4-MG patients were positive in 14.6% and 16.4% respectively. Most importantly, 13.4% (50/372) of the tSN-MG patients were also titin antibody positive. None of the 121 healthy controls or the 90 myopathy patients, and only 3.6% (7/193) of other neurological disease patients were positive. We thus propose that the present titin antibody RIPA is a useful tool for serological MG diagnosis of tSN patients.
- Klíčová slova
- Autoantibodies, Diagnosis, Myasthenia gravis, Radioimmunoprecipitation assay, Seronegative, Titin,
- MeSH
- autoprotilátky krev MeSH
- ELISA MeSH
- konektin imunologie MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- myasthenia gravis krev diagnóza epidemiologie MeSH
- proteiny související s LDL-receptory imunologie MeSH
- radioimunoprecipitační analýza MeSH
- receptory cholinergní imunologie MeSH
- tyrosinkinasové receptory imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- autoprotilátky MeSH
- konektin MeSH
- LRP4 protein, human MeSH Prohlížeč
- MUSK protein, human MeSH Prohlížeč
- proteiny související s LDL-receptory MeSH
- receptory cholinergní MeSH
- tyrosinkinasové receptory MeSH
The latest therapeutic approaches to Alzheimer disease are using intravenous immunoglobulin (IVIG) products. Therefore, the detailed characterization of target-specific antibodies naturally occurring in IVIG products is beneficial. We have focused on characterization of antibodies isolated against tau protein, a biomarker of Alzheimer's disease, from Flebogamma IVIG product. The analysis of IgG subclass distribution indicated skewing toward IgG3 in anti-tau-enriched IgG fraction. The evaluation of their reactivity and avidity with several recombinant tau forms was performed by ELISA and blotting techniques. Truncated non-phosphorylated tau protein (amino acids 155-421) demonstrated the highest reactivity and avidity index. We provide the first detailed insight into the reactivity of isolated natural antibodies against tau protein.
- Klíčová slova
- Alzheimer disease, Avidity, Immunoreactivity, Intravenous immunoglobulins, Natural antibodies, Tau protein,
- MeSH
- epitopy chemie MeSH
- imunoglobulin G imunologie izolace a purifikace MeSH
- imunosorpční techniky MeSH
- intravenózní imunoglobuliny chemie imunologie MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- peptidy imunologie MeSH
- proteiny tau imunologie MeSH
- terciární struktura proteinů MeSH
- vazba proteinů imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- epitopy MeSH
- imunoglobulin G MeSH
- intravenózní imunoglobuliny MeSH
- peptidy MeSH
- proteiny tau MeSH
