The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.
- MeSH
- adjuvancia imunologická MeSH
- aplikace intranazální MeSH
- chitosan * chemie MeSH
- glykoproteiny MeSH
- imunizace MeSH
- imunoglobulin A MeSH
- Muromegalovirus * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice * chemie MeSH
- slizniční imunita MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- biologické markery MeSH
- budesonid škodlivé účinky MeSH
- glomerulus patologie MeSH
- IgA nefropatie * diagnóza farmakoterapie patologie MeSH
- imunoglobulin A MeSH
- lidé MeSH
- proteinurie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied. METHODS: We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first-line treatment. Fifty-five patients were evaluated again after the treatment with CIT. RESULTS: We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1. CONCLUSIONS: CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction.
- MeSH
- chronická lymfatická leukemie * farmakoterapie krev imunologie mortalita MeSH
- dospělí MeSH
- imunoglobulin A * krev MeSH
- imunoterapie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- IgA nefropatie * farmakoterapie MeSH
- imunoglobulin A MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Secretory (S) IgA antibodies against severe acute respiratory syndrome (SARS)-CoV-2 are induced in saliva and upper respiratory tract (URT) secretions by natural infection and may be critical in determining the outcome of initial infection. Secretory IgA1 (SIgA1) is the predominant isotype of antibodies in these secretions. Neutralization of SARS-CoV-2 is most effectively accomplished by polymeric antibodies such as SIgA. We hypothesize that cleavage of SIgA1 antibodies against SARS-CoV-2 by unique bacterial IgA1 proteases to univalent Fabα antibody fragments with diminished virus neutralizing activity would facilitate the descent of the virus into the lungs to cause serious disease and also enhance its airborne transmission to others. Recent studies of the nasopharyngeal microbiota of patients with SARS-CoV-2 infection have revealed significant increases in the proportions of IgA1 protease-producing bacteria in comparison with healthy subjects. Similar considerations might apply also to other respiratory viral infections including influenza, possibly explaining the original attribution of influenza to Haemophilus influenzae, which produces IgA1 protease.
- MeSH
- Bacteria enzymologie MeSH
- COVID-19 * přenos imunologie virologie mikrobiologie MeSH
- Haemophilus influenzae enzymologie imunologie MeSH
- imunoglobulin A sekreční * metabolismus MeSH
- imunoglobulin A imunologie MeSH
- lidé MeSH
- nazofarynx mikrobiologie virologie MeSH
- neutralizující protilátky imunologie MeSH
- protilátky virové imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- serinové endopeptidasy metabolismus imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Celiakie (celiakální sprue, glutenová enteropatie) je celoživotní autoimunitní onemocnění, vyvolané nesnášenlivostí glutenu. V rámci dia- gnostiky je doporučen tzv. cílený screening u osob se symptomy, které mají souvislost s touto chorobou. Prvními provedenými sérologickými testy v rámci tohoto screeningu by mělo být dle aktuálních doporučení ESPGHAN stanovení celkové koncentrace IgA a stanovení koncentrace protilátek proti tkáňové transglutamináze (anti tTGA) ve třídě IgA. Cílem práce bylo zhodnotit efektivitu těchto vyšetření u dětských pacientů s ohledem na jejich věk a zdokumentovat, které symptomy u pacientů s pozitivní anti tTGA převažují. V souboru 4 104 pacientů ve věku 1–18 let, kteří byli vyšetřeni v období od 5/ 2021 do 5/2023, byl zjištěn pozitivní výsledek u 56 z nich (1,36 %). U 29 pacientů se jednalo o nově diagnostikovanou celiakii, 20 pacientů splňovalo kritéria pro cílený screening, 9 pacientů bylo v kontextu celiakie asymptomatických. Z příznaků převažovaly extraintestinální obtíže nad obtížemi gastrointestinálními. Otázkou zůstává, zda tyto sérologické testy provádět nezávisle na věku dítěte. V uvedeném časovém období jsme nezjistili pozitivní hodnotu anti tTGA IgA u žádného z 345 vyšetřených dětí do věku dvou let. Z našich výsledků vyplývá doporučení řídit se pro stanovení spodní věkové hranice pro provedení anti tTGA IgA individuálně u každého pacienta dobou, kdy došlo k zařazení glutenu do stravy.
Coeliac disease (coeliac sprue, gluten enteropathy) is a lifelong autoimmune disease caused by gluten intolerance. As part of the diagnosis, so- -called targeted screening is recommended for people having symptoms relating to the disease. Based on current ESPGHAN recommendations, the initial screening serological tests are total IgA levels and anti-tissue transglutaminase antibodies (anti-tTGA) IgA. The aim of the study was the evaluation of effectiveness of these examinations, performed to paediatric patients (with regard to their age) and to document the prevailing symptoms experienced by patients with positive anti-tTGA IgA. In a group of 4,104 patients aged 1–18 years examined between 5/21 to 5/23, anti-tTGA IgA was positive in 56 (1,36 %). Twenty-nine patients were newly diagnosed with coeliac disease (20 patients met the targeted screening criteria, 9 were asymptomatic). From the symptoms perspective, extra-intestinal symptomatology pre- vailed over gastrointestinal ones. To this day, performing serological tests regardless of the child‘s age remains a controversial topic. There has been no positive value detected by anti-tTGA IgA in any child below 2 years of age (out of 345 patients tested within the study period). Based on our research, and in order to determine the appropriate lower age limit for anti-tGA IgA screening, we recommend taking into account the time of gluten introduction into the child‘s diet individually.
- MeSH
- bezlepková dieta MeSH
- biopsie metody MeSH
- celiakie * diagnóza dietoterapie imunologie prevence a kontrola MeSH
- dítě MeSH
- gluteny imunologie škodlivé účinky MeSH
- imunoglobulin A analýza MeSH
- lidé MeSH
- protein-glutamin:amin-gama-glutamyltransferasa 2 analýza antagonisté a inhibitory MeSH
- screeningové diagnostické programy * MeSH
- sérologické testy MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická profylaxe MeSH
- hlášení nemocí MeSH
- imunoglobulin A krev MeSH
- imunoglobulin G krev MeSH
- pertuse * diagnóza terapie MeSH
- primární prevence MeSH
- sérologické testy MeSH
- vakcína proti záškrtu, tetanu a černému kašli MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Celiac disease is a common gastroenterological illness. Current diagnostics of the disease are based on serological markers and histology of duodenal biopsies. Hitherto, a strict gluten-free diet is the only effective treatment and is necessary for good control of the disease. Serological tests in current use have very high specificity and sensitivity for diagnostics, but in follow-up they have some limitations. Their levels do not accurately reflect mucosal healing, and they are unable to detect minimal transgressions in the diet. This problem is significant in patients with IgA deficiency, and there exist no robust follow-up tools for monitoring these patients' adherence to treatment. For their follow-up, we currently use IgG-based tests, and these antibodies persist for a long time even when a patient has stopped consuming gluten. More accurate and specific biomarkers are definitely needed. Adherence to a gluten-free diet is essential not only for intestinal mucosa healing and alleviation of symptoms but also for preventing complications associated with celiac disease. Here, we summarize current evidence regarding noninvasive biomarkers potentially useful for follow-up not only of patients with IgA deficiency but for all patients with celiac disease. We describe several very promising biomarkers with potential to be part of clinical practice in the near future.
- MeSH
- bezlepková dieta MeSH
- biologické markery MeSH
- celiakie * MeSH
- deficience IgA * MeSH
- gluteny MeSH
- imunoglobulin A MeSH
- lidé MeSH
- následné studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.
- MeSH
- galaktosa MeSH
- IgA nefropatie * diagnóza MeSH
- imunoglobulin A MeSH
- imunokomplex MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
