Given its myeloid-restricted expression, myeloperoxidase (MPO) is typically used for lineage assignment (myeloid vs. lymphoid) during acute leukaemia (AL) diagnostics. In the present study, a robust flow cytometric definition for MPO positivity was established based on the standardised EuroFlow protocols, the standardised Acute Leukaemia Orientation Tube and 1734 multicentre AL cases (with confirmed assay stability). The best diagnostic performance was achieved by defining MPO positivity as ≥20% of the AL cells exceeding a lymphocyte-based threshold. The methodology employed should be applicable to any form of standardised flow cytometry.
- MeSH
- akutní nemoc MeSH
- imunofenotypizace normy MeSH
- leukemie * diagnóza enzymologie imunologie MeSH
- lidé MeSH
- nádorové proteiny * krev imunologie MeSH
- peroxidasa * krev imunologie MeSH
- průtoková cytometrie normy MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- MeSH
- azathioprin terapeutické užití MeSH
- cyklofosfamid terapeutické užití MeSH
- granulomatóza s polyangiitidou komplikace farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace farmakoterapie MeSH
- myeloblastin imunologie MeSH
- nemoci ledvin etiologie patofyziologie MeSH
- peroxidasa imunologie MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
- recidiva MeSH
- rituximab terapeutické užití MeSH
- udržovací chemoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods: Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results: A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); P < 0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO:PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions: The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.
- MeSH
- ANCA-asociované vaskulitidy krev epidemiologie imunologie MeSH
- biopsie MeSH
- demografie MeSH
- glomerulonefritida krev imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myeloblastin imunologie MeSH
- peroxidasa imunologie MeSH
- protilátky proti cytoplazmě neutrofilů imunologie MeSH
- registrace MeSH
- senioři MeSH
- séroskupina MeSH
- specificita protilátek MeSH
- zeměpis MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
- Itálie MeSH
- Norsko MeSH
- Spojené království MeSH
- Spojené státy americké MeSH
- Švédsko MeSH
OBJECTIVES: To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. METHODS: The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥ 1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). RESULTS: 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6 ± 13.9 vs. 46.8 ± 17.3 years), had higher Birmingham vasculitis activity score (19.5 ± 9.1 vs. 16.9 ± 7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). CONCLUSIONS: Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations.
- MeSH
- dospělí MeSH
- granulomatóza s polyangiitidou komplikace epidemiologie imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace epidemiologie imunologie MeSH
- myeloblastin imunologie MeSH
- nemoci ledvin etiologie MeSH
- otorinolaryngologické nemoci etiologie MeSH
- peroxidasa imunologie MeSH
- pozorovací studie jako téma * MeSH
- protilátky proti cytoplazmě neutrofilů imunologie MeSH
- randomizované kontrolované studie jako téma * MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- věkové rozložení MeSH
- výběr pacientů 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
- Research Support, N.I.H., Extramural MeSH
Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Recently, small cationic α-defensin molecules have been implicated in the pathogenesis of certain inflammatory and autoimmune diseases. The purpose of this study was to assess the α-defensin expression in patients with T1D and elucidate the cellular source of their production. Our results show that 30% of patients exhibit increased levels of α-defensin mRNAs in their capillary blood. Quantitative RT-PCR performed on FACS-sorted granulocytes identified CD15(dull)/CD14(weak) population as the cellular source of α-defensins. Surprisingly, this granulocyte subpopulation displayed augmentation of α-defensin expression in all T1D patients tested. The determination of cell surface markers, expression of cell-specific genes and confocal microscopy identified CD15(dull)/CD14(weak) cells as eosinophils. The presence of transcriptionally active eosinophils in diabetic patients suggests that eosinophils could be a part of an intricate innate immune cellular network involved in the development of diabetes.
- MeSH
- alfa-defensiny krev genetika imunologie MeSH
- antigen Lewis X imunologie MeSH
- antigeny CD14 imunologie MeSH
- autoimunita MeSH
- beta-buňky imunologie metabolismus patologie MeSH
- diabetes mellitus 1. typu krev genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- eozinofily imunologie metabolismus patologie MeSH
- exprese genu MeSH
- imunologická tolerance MeSH
- lidé MeSH
- messenger RNA biosyntéza MeSH
- mladiství MeSH
- peroxidasa krev genetika imunologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- předškolní dítě MeSH
- přirozená imunita MeSH
- průtoková cytometrie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- autoimunitní tyreoiditida diagnóza komplikace krev MeSH
- autoprotilátky krev MeSH
- biologické markery krev MeSH
- dospělí MeSH
- financování organizované MeSH
- hypotyreóza diagnóza epidemiologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- morbidní obezita epidemiologie krev MeSH
- peroxidasa imunologie MeSH
- prediktivní hodnota testů MeSH
- prevalence MeSH
- tělesná hmotnost MeSH
- thyreotropin krev MeSH
- thyroxin krev MeSH
- trijodthyronin krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- souhrny MeSH
AAV are a group of systemic immune-mediated diseases with a strong and highly specific association with ANCA. In recent years, there has been increasing evidence that ANCA might play a direct pathogenic role in triggering AAV. Nevertheless, effectors of cell-mediated immunity prevail in the inflammation sites in patients with AAV. Numerous studies found increased markers of T-cell activation in AAV. Moreover, this activation persisted even in remission and despite treatment. Finally, successful therapeutic attempts using T cell-directed treatment were also reported. There has therefore been substantial evidence that T cells are involved in the pathogenesis of AAV, even though the exact mechanisms are yet to be elucidated. In this review, recent findings on the contribution of T cells to the pathogenic processes in AAV will be briefly summarized. Special emphasis will be placed on the Th1/Th2 concept, the role of T-regulatory cells, and the role of effector memory T cells in the pathogenesis of AAV.
- MeSH
- aktivace lymfocytů MeSH
- cytokiny imunologie metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- imunologická paměť MeSH
- lidé MeSH
- myeloblastin imunologie metabolismus MeSH
- peroxidasa imunologie metabolismus MeSH
- protilátky proti cytoplazmě neutrofilů imunologie krev MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- Th1 buňky imunologie metabolismus MeSH
- Th2 buňky imunologie metabolismus MeSH
- vaskulitida imunologie metabolismus terapie MeSH
- Check Tag
- lidé MeSH
Autoimunní onemocnění štítné žlázy jsou častou diagnózou v ordinacích dětských endokrinologů. Tato onemocnění se týkají hlavně dospívajících a zvláště dívek, i když nejsou výjimkou ani v mladším školním věku. Ve svém článku se chci zmínit hlavně o jednotlivých typech protilátek, které s autoimunním onemocněním štítné žlázy souvisí, a které běžně v ordinacích (ať už endokrinologických, nebo ordinacích PLDD) můžeme vyšetřovat. V závěru článku stručně proberu jednotlivá autoimunní onemocnění štítné žlázy u dětí, a to hlavně s ohledem na jejich etiopatogenezi.
