Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis1. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta2. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency3,4, and in patients diagnosed with coeliac disease5-7. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.

• MeSH
• ameloblasty metabolismus   MeSH
• amelogenesis imperfecta * komplikace   imunologie   MeSH
• antigeny imunologie   metabolismus   MeSH
• autoimunitní polyglandulární syndromy * komplikace   imunologie   MeSH
• autoprotilátky * imunologie   MeSH
• celiakie * komplikace   imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• lidé MeSH
• protein AIRE nedostatek   MeSH
• proteiny imunologie   metabolismus   MeSH
• střeva imunologie   metabolismus   MeSH
• zubní sklovina imunologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Diagnostické postupy používané k průkazu onemocnění COVID-19 zahrnují klinickou anamnézu, PCR test přítomnosti SARS-CoV-2 a průkaz protilátek proti viru. Kombinací těchto metod je možné zjistit séroprevalenci zdravotnických pracovníků na SARS-CoV-2. Cílem práce bylo stanovení výskytu protilátek proti SARS-CoV-2 u zdravotnických pracovníků po 6–8 týdnech od prvního nálezu COVID-19 v České republice. Bylo vyšetřeno 269 osob (187 žen, 82 mužů) s věkovým průměrem 45,9 roku (21–71 let). Pomocí dotazníků bylo zjišťováno, zda osoby byly v zahraničí a zda se u nich vyskytovaly klinické příznaky typické pro respirační onemocnění. U všech byla zjišťována přítomnost IgG protilátek v séru. V případě pozitivního IgG bylo doplněno vyšetření IgA a PCR vyšetření přítomnosti SARS-CoV-2 ve stěru. Ke stanovení protilátek byly použity testy ELISA SARS-CoV-2-IgG a SARS-CoV-2-IgA firmy Euroimmun. Klinické příznaky udávalo 17 % osob, v zahraničí bylo 35,8 % osob. IgG-pozitivních bylo 5 z 269 testovaných osob (1,85 %). Pozitivní IgA a hraničně pozitivní IgG měla 1 osoba (0,37 %). Pozitivní výsledek PCR měla 1 osoba. Protilátky proti SARS-CoV-2 tak byly zjištěny u 2,22 % vyšetřovaných osob. V článku jsou diskutovány limity testování, které jsou ovlivněny jak zvoleným typem vyšetření, tak nízkým výskytem onemocnění ve společnosti.

Diagnostic approaches to COVID-19 include clinical history, PCR tests for the presence of SARS-CoV-2 virus and detection of antibodies. By combining these three approaches, the seroprevalence of anti–SARS-CoV-2 antibodies can be examined in healthcare teams.The aim of the study was to examine the seroprevalence of anti–SARS-CoV-2 antibodies in a population of healthcare professionals 6–8 weeks after the first COVID-19 case was detected in the Czech Republic. A total of 269 subjects were enrolled in the study (187 women, 82 men) with a median age of 45.9 years (21 – 71 years). We used a questionnaire to ascertain travel history and clinical signs of any respiratory tract infection. Blood samples were collected, and IgG levels were analysed in all samples. The level of IgA antibodies was analysed in those positive for IgG. PCR testing was performed in cases testing positive for presence of antibodies. The enzyme-linked immunosorbent assay (ELISA) test system for SARS-CoV-2 from Euroimmun (Germany) was used to analyse immunoglobulin levels.17 % of the tested cohort reported symptoms compatible with COVID-19 and 35.8 % reported history of international travel. There were 5 subjects positive IgG cases (of 269; 1.85 %), and one IgA positive and IgG borderline positive subject (0.37 %). There was only one PCR positive subject. Anti SARS-CoV-2 antibodies were thus detected in 2.22% of participating health professionals. This article shows the pitfalls of the testing methods and highlights the necessity of using a correct testing algorithm, considering the character of the tested population and the expected low prevalence.

• MeSH
• Betacoronavirus * imunologie   MeSH
• COVID-19 * diagnóza   MeSH
• ELISA MeSH
• imunoglobulin A imunologie   krev   MeSH
• imunoglobulin G imunologie   krev   MeSH
• koronavirové infekce diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• prediktivní hodnota testů MeSH
• protilátky krev   MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• séroepidemiologické studie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

V Domově se zvláštním režimem v Břevnici bylo v březnu 2020 koronavirem SARS-CoV-2 infikováno 21 z 23 seniorů a 3 z nich v souvislosti s infekcí zemřeli. Předložená studie monitoruje tvorbu protilátek u této skupiny seniorů v období od začátku dubna do listopadu, tedy 1–8 měsíců po prodělaném onemocnění. Studie také srovnává několik různých metod stanovení protilátek. Protilátky byly stanovovány opakovaně, vždy s odstupem několika týdnů, a to jak virus-neutralizačním testem, tak metodami ECLIA Roche (celkové imunoglobuliny), CMIA Abbott (IgG) a ELISA Euroimmun (IgG a IgA). Neutralizační protilátky byly detekovány u 18 z 20 osob v sérech odebraných po 6 měsících od prodělané infekce. Vysoké hodnoty neutralizačních protilátek korelovaly s vyššími hodnotami imunoglobulinů v ostatních testech a predikovaly vzestup protilátek IgG v podzimním období, kdy probíhala druhá vlna epidemie. Na podzim v domově neonemocněl žádný klient ani zaměstnanec, přestože v kraji Vysočina bylo tou dobou více než 5 % osob s pozitivním PCR testem. Infekce novým koronavirem nebyla zjištěna ani antigenními testy. Tato studie ukazuje, že senioři si po prodělaném onemocnění COVID-19 tvoří ochranné protilátky, a jsou tedy zřejmě imunní vůči reinfekci po dobu delší než 8 měsíců. Na základě tohoto zjištění bychom chtěli otevřít diskusi o testování séroprevalence v domovech seniorů a podobných zařízeních, o úpravě epidemiologického režimu v závislosti na rizicích infekce a o případných očkovacích schématech v domovech seniorů.

In the nursing home in Břevnice, 21 out of 23 seniors were infected with the SARS-CoV-2 virus in the spring of 2020. Three of them died from the infection. This study monitors the antibodies formation in group of seniors who have overcome the infection. Between April and November (1-8 months after the infection), the antibodies were measured repeatedly within the period of several weeks. The virus neutralizing tests was used as well as the ECLIA assay by Roche (total immunoglobulins), CMIA assay by Abbott (IgG) and ELISA assay by Euroimmun (IgG and IgA). Six months from the infection, neutralizing antibodies were detected in 18 out of 20 seniors. High levels of neutralizing antibodies correlated with higher levels of immunoglobulins and were a good predictor of an increase of IgG in the autumn during the second wave of the epidemic in the Czech Republic. During the autumn wave, neither any of the clients, nor any staff contracted the virus, although the prevalence of PCR positivity in the Vysočina region reached around 5 %. The antigen tests also came out all negative. This study shows that in the senior population, the production of protective antibodies follows a normal pattern, and the seniors are probably immune to a repeated infection for at least 8 months from the first infection. Based on these results, we would like to open the discussion on the testing for seroprevalence in nursing homes, possible changes to the epidemiologic regime in relation to the risk of infection, and about vaccination schemes in these centers.

• MeSH
• COVID-19 * diagnóza   imunologie   MeSH
• demence MeSH
• domovy pro seniory * MeSH
• imunoglobulin A imunologie   krev   MeSH
• imunoglobulin G imunologie   krev   MeSH
• imunoglobulin M imunologie   krev   MeSH
• lidé MeSH
• protilátky virové krev   MeSH
• reinfekce MeSH
• SARS-CoV-2 patogenita   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testování na COVID-19 metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

Common Variable Immunodeficiency (CVID) is the most frequent symptomatic immune disorder characterized by reduced serum immunoglobulins. Patients often suffer from infectious and serious non-infectious complications which impact their life tremendously. The monogenic cause has been revealed in a minority of patients so far, indicating the role of multiple genes and environmental factors in CVID etiology. Using 16S and ITS rRNA amplicon sequencing, we analyzed the bacterial and fungal gut microbiota, respectively, in a group of 55 participants constituting of CVID patients and matched healthy controls including 16 case-control pairs living in the same household, to explore possible associations between gut microbiota composition and disease phenotype. We revealed less diverse and significantly altered bacterial but not fungal gut microbiota in CVID patients, which additionally appeared to be associated with a more severe disease phenotype. The factor of sharing the same household impacted both bacterial and fungal microbiome data significantly, although not as strongly as CVID diagnosis in bacterial assessment. Overall, our results suggest that gut bacterial microbiota is altered in CVID patients and may be one of the missing environmental drivers contributing to some of the symptoms and disease severity. Paired samples serving as controls will provide a better resolution between disease-related dysbiosis and other environmental confounders in future studies.

• MeSH
• Bacteria klasifikace   genetika   imunologie   MeSH
• běžná variabilní imunodeficience imunologie   mikrobiologie   MeSH
• biodiverzita MeSH
• dospělí MeSH
• feces mikrobiologie   MeSH
• houby klasifikace   genetika   imunologie   MeSH
• imunoglobulin A krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mykobiom * MeSH
• senioři MeSH
• střevní mikroflóra * imunologie   MeSH
• studie případů a kontrol MeSH
• zdraví rodiny MeSH
• zdravotní stav MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20-40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.

• MeSH
• chronická renální insuficience imunologie   MeSH
• glomerulonefritida imunologie   MeSH
• IgA nefropatie imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• komplement C3 imunologie   MeSH
• komplement C5 imunologie   MeSH
• ledviny imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has serious outcomes with end-stage renal disease developing in 30-50% of patients. The diagnosis requires renal biopsy. Due to its inherent risks, non-invasive approaches are needed. METHODS: We evaluated 91 Czech patients with biopsy-proven IgAN who were assessed at time of diagnosis for estimated glomerular filtration rate (eGFR), proteinuria, microscopic hematuria, and hypertension, and then followed prospectively. Serum samples collected at diagnosis were analyzed for galactose-deficient IgA1 (Gd-IgA1) using new native-IgA1 and established neuraminidase-treated-IgA1 tests, Gd-IgA1-specific IgG autoantibodies, discriminant analysis and logistic regression model assessed correlations with renal function and Oxford classification (MEST score). RESULTS: Serum levels of native (P <0.005) and neuraminidase-treated (P <0.005) Gd-IgA1 were associated with the rate of eGFR decline. A higher relative degree of galactose deficiency in native serum IgA1 predicted a faster eGFR decline and poor renal survival (P <0.005). However, Gd-IgA1 has not differentiated patients with low vs. high baseline eGFR. Furthermore, patients with high baseline eGFR that was maintained during follow-up were characterized by low serum levels of Gd-IgA1-specific IgG autoantibodies (P = 0.003). CONCLUSIONS: Including levels of native and neuraminidase-treated Gd-IgA1 and Gd-IgA1-specific autoantibodies at diagnosis may aid in the prognostication of disease progression in Czech patients with IgAN. Future tests will assess utility of these biomarkers in larger patients cohorts from geographically distinct areas.

• MeSH
• autoprotilátky krev   imunologie   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• galaktosa krev   imunologie   MeSH
• IgA nefropatie krev   diagnóza   imunologie   mortalita   MeSH
• imunoglobulin A krev   imunologie   MeSH
• lidé MeSH
• následné studie MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• Klíčová slova
• COLIFANT NEWBORN,
• MeSH
• anamnéza MeSH
• časná přecitlivělost * farmakoterapie   krev   prevence a kontrola   MeSH
• dítě MeSH
• Escherichia coli imunologie   MeSH
• fetální krev imunologie   MeSH
• imunoglobulin A analýza   imunologie   MeSH
• imunoglobulin E analýza   MeSH
• kojenec MeSH
• lidé MeSH
• morbidita MeSH
• novorozenec MeSH
• odběr fetální krve MeSH
• střevní mikroflóra imunologie   účinky léků   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH

The alcohol-soluble fraction of wheat gluten (gliadins) induces in genetically susceptible individuals immunologically mediated celiac disease (CLD). However, gliadins and related cereal proteins are not unique foodstuff targets of CLD patients´ immune system. Non-gluten wheat alpha-amylase inhibitor 0.19 (AAI 0.19) has been found to be capable of activating human monocyte-derived dendritic cells and inducing pro-inflammatory status in intestinal mucosa of patients with celiac disease (CLD). The possible contribution of this reactivity in incomplete remission of CLD patients on a gluten-free diet (GFD) is matter of contention. In an attempt to characterize the antigenicity of AAI 0.19 in patients with active CLD, patients on a GFD and healthy controls we developed ELISA employing wheat recombinant AAI 0.19. Using this test we revealed a significant (P<0.001) elevation of IgA anti-AAI 0.19 antibodies (Ab) in patients with active CLD (12 out of 30 patients were seropositive) but also in CLD patients on a GFD (15/46), in contrast to healthy controls (2/59). Anti-AAI 0.19 IgG Ab levels were increased (P<0.001) only in patients with active CLD (14/30) in contrast to the controls. Interestingly, the levels of anti-AAI 0.19 IgG Ab were decreased in CLD patients on a GFD (P<0.001, 1/46) compared to the controls (1/59). Notably, 20 out of 30 patients with active CLD were positive either for IgA or for IgG anti-AAI 0.19 Ab. Thus, the majority of CLD patients developed a robust IgA and IgG Ab response against AAI 0.19. These findings may contribute to the broadening of the knowledge about CLD pathogenesis.

• MeSH
• celiakie krev   diagnóza   imunologie   MeSH
• dospělí MeSH
• imunoglobulin A krev   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protilátky anti-idiotypické krev   imunologie   MeSH
• rostlinné proteiny * imunologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIMS: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended. METHODS: The relationship between the corticosteroid therapy and serum levels of IgA, aberrantly O-glycosylated IgA1, IgA-containing immune complexes and their mesangioproliferative activity was analyzed in IgA nephropathy patients and disease and healthy controls. RESULTS: Prednisone therapy significantly reduced proteinuria and levels of serum IgA, galactose-deficient IgA1, and IgA-IgG immune complexes in IgA nephropathy patients and thus reduced differences in all of the above parameters between IgAN patients and control groups. A moderate but not significant reduction of mesangioproliferative potential of IgA-IgG immune complexes and IgA sialylation was detected. CONCLUSION: The prednisone therapy reduces overall aberrancy in IgA1 O-glycosylation in IgA nephropathy patients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients.

• MeSH
• glukokortikoidy farmakologie   terapeutické užití   MeSH
• glykosylace účinky léků   MeSH
• IgA nefropatie diagnóza   farmakoterapie   MeSH
• imunoglobulin A krev   imunologie   metabolismus   MeSH
• imunokomplex krev   MeSH
• lidé MeSH
• prednison terapeutické užití   MeSH
• prognóza MeSH
• protilátky krev   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an "immune evasion" milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-κB. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.

• MeSH
• antikarcinogenní látky farmakologie   MeSH
• autofagie účinky léků   imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• imunologické faktory farmakologie   MeSH
• imunosupresiva farmakologie   MeSH
• infekce farmakoterapie   imunologie   MeSH
• lidé MeSH
• signální transdukce účinky léků   imunologie   MeSH
• trichotheceny chemie   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH