BACKGROUND: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. METHODS: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. RESULTS: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15-34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9-19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17-82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). CONCLUSIONS: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

• Klíčová slova
• ANCA vasculitis, Immunosuppression, Kidney biopsy,
• MeSH
• analýza přežití MeSH
• ANCA-asociované vaskulitidy imunologie   mortalita   patologie   MeSH
• atrofie imunologie   patologie   MeSH
• biopsie MeSH
• chronické selhání ledvin krev   epidemiologie   imunologie   MeSH
• fibróza MeSH
• glomerulonefritida imunologie   mortalita   patologie   MeSH
• hodnoty glomerulární filtrace MeSH
• ledviny krevní zásobení   imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protilátky proti cytoplazmě neutrofilů krev   imunologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.

• Klíčová slova
• Goodpasture syndrome, anti-GBM disease, anti–neutrophil cytoplasm antibody, glomerulonephritis, vasculitis,
• MeSH
• ANCA-asociované vaskulitidy krev   imunologie   mortalita   terapie   MeSH
• antirenální glomerulonefritida krev   imunologie   mortalita   terapie   MeSH
• autoprotilátky krev   MeSH
• chronické selhání ledvin krev   imunologie   mortalita   terapie   MeSH
• dialýza ledvin MeSH
• dítě MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• krvácení imunologie   MeSH
• ledviny imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• plicní nemoci imunologie   MeSH
• přežití bez známek nemoci MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antiglomerular basement membrane antibody MeSH Prohlížeč
• autoprotilátky MeSH
• imunosupresiva MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients. Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature. FINDINGS: The 56 children with GPA/WG were predominantly females (68%) and Caucasians (82%) with a median age at disease onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most frequent organ systems involved before/at the time of diagnosis were ears, nose, throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA-PR3 positive, while haematuria/proteinuria was present in > 50% of the children. In adult series, the frequency of female involvement ranged from 29% to 50% with lower frequencies of constitutional (fever, weight loss), ears, nose, throat (oral/nasal ulceration, otitis/aural discharge), respiratory (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher frequency of conductive hearing loss than in this paediatric series. CONCLUSIONS: Paediatric patients compared to adults with GPA/WG have similar pattern of clinical manifestations but different frequencies of organ involvement.

• Klíčová slova
• Clinical picture of disease, Clinical study, Comparison with literature, Granulomatosis with polyangiitis, Wegener’s granulomatosis,
• MeSH
• biopsie MeSH
• dítě MeSH
• dospělí MeSH
• granulom dýchacího systému * imunologie   patologie   MeSH
• granulomatóza s polyangiitidou * diagnóza   epidemiologie   imunologie   patofyziologie   MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• mladiství MeSH
• orgánová specificita imunologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• věk při počátku nemoci MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

• MeSH
• adalimumab MeSH
• ankylózující spondylitida komplikace   farmakoterapie   MeSH
• fokálně segmentální glomeruloskleróza komplikace   diagnóza   imunologie   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoglobulin G krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci mediastina komplikace   diagnóza   imunologie   MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adalimumab MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• TNF-alfa MeSH

Inconsistencies in ANCA (anti-neutrophil cytoplasm autoantibodies) and other NSA (neutrophil-specific autoantibodies) terminology frequently cause incorrect indications, choices, applications and interpretations of ANCA diagnostics in routine practice, except for ANCA-associated vasculitis. A review of the current knowledge and the authors' personal experiences based on routine assessments of ANCA and other NSA are documented and presented. A better understanding of the principles and mechanisms of ANCA and other NSA responses and determination, as well as unification of their terminology could result in improvements in indications, applications and the interpretation of ANCA diagnostics in diseases other than vasculitis, especially in IBD (inflammatory bowel diseases), AILD (autoimmune liver diseases), CTD (connective tissue diseases) and other chronic neutrophil-mediated inflammatory diseases.

• MeSH
• autoprotilátky MeSH
• lidé MeSH
• neutrofily imunologie   MeSH
• protilátky proti cytoplazmě neutrofilů * krev   MeSH
• terminologie jako téma MeSH
• zánět krev   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• autoprotilátky MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH

OBJECTIVES: ANCA-associated vasculitis (AAV) is an inflammatory disorder of small- to medium-sized vessels with relapsing/remitting progression. Microvascular endothelial injury is a major feature of AAV. Circulating endothelial progenitor cells (EPCs) may provide an endogenous repair mechanism to counteract ongoing endothelial damage. We hypothesized that decreased capacity for endothelial regeneration paralleled by low EPC numbers could increase the risk of relapse in patients with AAV. METHODS: The number of circulating EPCs was determined by a colony-forming assay in a cohort of 41 patients with AAV. The patients were stratified into three subgroups according to the initial EPC count (low, medium and high) and prospectively followed. The primary goal was to determine the association between baseline EPC level and the time to the first relapse of the disease. RESULTS: A total of 19 (46%) patients relapsed during the study period. The cumulative relapse-free survival increased stepwise across three increasing baseline levels of EPCs (P = 0.013). EPC levels were not predictive of progression of renal disease, number of organs involved or death from any cause. CONCLUSION: Low numbers of EPCs are associated with increased propensity for early relapse of AAV.

• MeSH
• autoimunitní nemoci krev   imunologie   MeSH
• dospělí MeSH
• endoteliální buňky patologie   MeSH
• epidemiologické metody MeSH
• glomerulonefritida krev   MeSH
• kmenové buňky patologie   MeSH
• kreatinin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet buněk MeSH
• prognóza MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• recidiva MeSH
• senioři MeSH
• vaskulitida krev   imunologie   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
• Názvy látek
• kreatinin MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

BACKGROUND AND AIMS: Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. METHODS: We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3+T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. RESULTS: When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p<0.01) and in remission (p<0.05). In remission, increased IFN-gamma production was also found (p<0.01). IL-10 production was higher in active patients than in patients in remission (p<0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p<0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. CONCLUSIONS: Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.

• MeSH
• cytokiny imunologie   MeSH
• dospělí MeSH
• interleukin-10 imunologie   MeSH
• interleukin-12 imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• protilátky proti cytoplazmě neutrofilů krev   imunologie   MeSH
• recidiva MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulitida imunologie   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
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• IL10 protein, human MeSH Prohlížeč
• interleukin-10 MeSH
• interleukin-12 MeSH
• protilátky proti cytoplazmě neutrofilů 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 krev   imunologie   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
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• myeloblastin MeSH
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

Nephrologists deal with a host of pathologic conditions involving renal and systemic endothelium. Both in native and transplanted kidneys, often the insult to the renal endothelium initiates the pathogenic process ultimately leading to the loss of organ function. Also, systemic atherosclerosis is accelerated in patients with renal dysfunction. In this review we would like to cover the possible role of CECs and their counterparts--circulating EPCs in the pathogenesis of endothelial dysfunction associated with chronic renal failure, ANCA-associated vasculitis, and progression of chronic renal disease.

• MeSH
• biologické markery MeSH
• chronické selhání ledvin patologie   MeSH
• endoteliální buňky fyziologie   MeSH
• kmenové buňky fyziologie   MeSH
• lidé MeSH
• počet buněk MeSH
• protilátky proti cytoplazmě neutrofilů krev   imunologie   MeSH
• transplantace ledvin patologie   MeSH
• vaskulitida etiologie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

BACKGROUND: Exposure to silica dust is considered to be one of etiological factors of antineutrophil cytoplasmic antibodies (ANCA) -associated vasculitis (AAV). METHODS: Subjects exposed to silica dust in Central Bohemia and followed in the Department of Occupational Medicine, Charles University, were selected for study. A group of 86 men exposed to SiO2 for at least 5 years were examined. The association between occupational exposure to silica dust and ANCA positivity is analyzed. RESULTS: The subjects had a mean age of 66.7 years, and mean exposure to silica of 22.3 years. ANCA were detected significantly more frequently in patients group (17.1%; P-ANCA 18x, C-ANCA 3x) than in controls (n = 28, mean age 64.2 years, P-ANCA 1x, i.e., 3.6%). ANCA positivity was found less frequently (7.1%) in the group with history of SiO2 exposure without signs of pronounced silicosis, than in the group with simple (30.3%) or complicated silicosis (36.0%). Odds ratio for ANCA positivity and relative risk estimate in patients with silicosis were highly significant. Among possible predictor factors for ANCA positivity, silicosis and tuberculosis were relevant. No typical AAV was present among the patients. CONCLUSION: Long-term silica exposure may be one of the exogenous factors contributing to ANCA production, however, silica exposure alone, without typical silicosis, was not associated with ANCA positivity.

• MeSH
• dospělí MeSH
• hornictví MeSH
• keramika škodlivé účinky   MeSH
• látky znečišťující vzduch v pracovním prostředí škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neparametrická statistika MeSH
• oxid křemičitý škodlivé účinky   MeSH
• pneumokonióza imunologie   MeSH
• prach MeSH
• pracovní expozice * MeSH
• protilátky proti cytoplazmě neutrofilů krev   imunologie   MeSH
• rozdělení chí kvadrát MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• silikóza komplikace   imunologie   MeSH
• vaskulitida etiologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch v pracovním prostředí MeSH
• oxid křemičitý MeSH
• prach MeSH
• protilátky proti cytoplazmě neutrofilů MeSH