ANCA-associated vasculitis (AAV) is a rare, but potentially severe autoimmune disease, even nowadays displaying increased mortality and morbidity. Finding early biomarkers of activity and prognosis is thus very important. Small extracellular vesicles (EVs) isolated from urine can be considered as a non-invasive source of biomarkers. We evaluated several protocols for urinary EV isolation. To eliminate contaminating non-vesicular proteins due to AAV associated proteinuria we used proteinase K treatment. We investigated the differences in proteomes of small EVs of patients with AAV compared to healthy controls by label-free LC-MS/MS. In parallel, we performed an analogous proteomic analysis of urine samples from identical patients. The study results showed significant differences and similarities in both EV and urine proteome, the latter one being highly affected by proteinuria. Using bioinformatics tools we explored differentially changed proteins and their related pathways with a focus on the pathophysiology of AAV. Our findings indicate significant regulation of Golgi enzymes, such as MAN1A1, which can be involved in T cell activation by N-glycans glycosylation and may thus play a key role in pathogenesis and diagnosis of AAV. SIGNIFICANCE: The present study explores for the first time the changes in proteomes of small extracellular vesicles and urine of patients with renal ANCA-associated vasculitis compared to healthy controls by label-free LC-MS/MS. Isolation of vesicles from proteinuric urine samples has been modified to minimize contamination by plasma proteins and to reduce co-isolation of extraluminal proteins. Differentially changed proteins and their related pathways with a role in the pathophysiology of AAV were described and discussed. The results could be helpful for the research of potential biomarkers in renal vasculitis associated with ANCA.

• Klíčová slova
• ANCA-associated vasculitis, Exosomes, N-glycosylation, Proteinuria, Small extracellular vesicles, Urinary proteomics,
• MeSH
• ANCA-asociované vaskulitidy * diagnóza   MeSH
• chromatografie kapalinová MeSH
• extracelulární vezikuly * MeSH
• lidé MeSH
• proteomika MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Introduction of the standard immunosuppressive treatment has dramatically changed the outcome of patients with both ANCA-associated vasculitis and lupus nephritis, transforming them from incurable diseases with very high short-term mortality to chronic debilitating diseases with much lower short-term, but still relatively high long-term, morbidity/mortality. Long-term morbidity with damage accumulating partly due to the adverse events of the available treatment (namely gonadal toxicity, malignancy, bone disease, cataracts, diabetes, and thromboembolic and cardiovascular disease) has become a major concern. Although cyclophosphamide-based regimens have been partly replaced by newer agents in both ANCA-associated vasculitis and lupus nephritis (namely rituximab or mycophenolate, respectively) their short-term and medium-term adverse events may not be significantly less frequent and we can only hope that new treatments will translate into better long-term outcomes including better long-term safety.

• MeSH
• ANCA-asociované vaskulitidy farmakoterapie   MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• nefritida při lupus erythematodes farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• imunosupresiva MeSH

ANCA-associated vasculitides (AAV) are small-vessel necrotizing vasculitides, with no or few immune deposits. They are usually associated with the presence of ANCA antibodies (AntiNeutrophil Cytoplasmic Antibody), targeted either against proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). ANCA-associated vasculitides include granulomatosis with polyangiitis (formerly Wegener's), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). The most commonly afflicted organs involve the lungs and the respiratory tract, ENT area, and the kidneys. Renal involvement typically manifests as pauci-immune necrotizing crescentic rapidly progressive glomerulonpehritis. Pulmo-renal syndrome with lung haemorrhage and deteriorating kidney function may be acutely life-threatening. Diagnostic methods include ANCA measurement, imaging methods and biopsy. Early recognition of the diagnosis and an early start of adequate treatment are necessary for a good outcome. The current treatment typically consists of corticosteroids and either cyclophoshapmide or rituximab (a monoclonal antibody directed against CD20 antigen). The addition of plasma exchange may be considered in severe cases. Rituximab is preferred for the treatment of all relapsing forms of this vasculitis.

• Klíčová slova
• ANCA, Biopsy, granulomatosis with polyangiitis, therapy, treatment, vasculitis,
• MeSH
• ANCA-asociované vaskulitidy * diagnóza   patologie   MeSH
• lidé MeSH
• protilátky proti cytoplazmě neutrofilů imunologie   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is the leading cause of rapidly progressive glomerulonephritis, which may follow an unfavorable disease course. Despite therapeutic advances, a number of patients with AAV will eventually develop end-stage renal disease (ESRD). Renal transplantation (RTx) is associated with a survival benefit and improves quality of life in patients with ESRD. SUMMARY: In recent years, RTx has been increasingly used also in patients with vasculitis. The posttransplant patient- and graft-survival rates in AAV were at least comparable to other diagnoses in most studies. Prior to transplantation, patients should be in stable remission for 12 months. Persistent ANCA positivity does not exclude patients from the waiting list. Even though the recurrence risk is generally low with modern posttransplant immunosuppression, including mycophenolate mofetil and tacrolimus, patients with AAV, particularly those with positive antiproteinase-3 ANCA who may have increased risk of relapse or recurrence of the disease, require constant surveillance. Similar to treatment of relapsing disease in the nontransplant setting, rituximab may become treatment of choice for posttransplant recurrences. Key Messages: RTx is the preferred renal replacement therapy of choice for AAV patients with ESRD. It is recommended that patients should be in remission for about 12 months prior to proceeding with RTx. ANCA positivity alone is not a contraindication for transplantation. The risk of relapse posttransplantation is minimal with currently used posttransplant immunosuppressive regimen.

• Klíčová slova
• Anti-neutrophil cytoplasmic antibody vasculitis, Recurrence risk, Renal transplantation,
• MeSH
• ANCA-asociované vaskulitidy chirurgie   MeSH
• dospělí MeSH
• lidé MeSH
• transplantace ledvin metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

OBJECTIVE: To investigate the occurrence of cardiovascular events (CVEs) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, China, Turkey, Russia, the United Kingdom, and the USA. METHODS: Patients with a definite diagnosis of AAV who were followed for ≥ 3 months and had sufficient documentation were included. Data on myocardial infarction (MI) and stroke were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Over a median follow-up of 62.0 months (IQR 22.6-100.0), CVEs (mostly MIs) occurred in 245 (10.7%) of 2286 patients with AAV, with a higher frequency in China and the UK. On multivariate regression analysis, older age (55-64.9 yrs, HR 2.93, 95% CI 1.99-4.31), smoking (HR 1.98, 95% CI 1.48-2.64), Chinese origin (HR 4.24, 95% CI 3.07-5.85), and pulmonary (HR 1.50, 95% CI 1.09-2.06) and kidney (HR 3.02, 95% CI 2.08-4.37) involvement were independent variables associated with a higher occurrence of CVEs. CONCLUSION: We showed that geographic region and both traditional and disease-specific (kidney involvement in particular) factors were independently associated with CVEs. Proper assessment and management of modifiable cardiovascular (CV) risk factors are essential for prevention of CV morbidity in patients with AAV.

• Klíčová slova
• ANCA-associated vasculitis, cardiovascular events, myocardial infarction, risk factors, stroke,
• MeSH
• ANCA-asociované vaskulitidy * MeSH
• ledviny MeSH
• lidé MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů * MeSH

• MeSH
• ANCA-asociované vaskulitidy * diagnóza   etiologie   patofyziologie   terapie   MeSH
• lidé MeSH
• nemoci ledvin * diagnóza   etiologie   patofyziologie   terapie   MeSH
• protilátky proti cytoplazmě neutrofilů analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

Incidence of ANCA antibodies in patients with systemic lupus erythematosus (SLE) is described in 24-31 %, but they are not related to the distribution and severity of organ involvement in SLE; the routine monitoring is not recommended. Overlap syndrome of systemic lupus erythematosus and ANCA associated vasculitis (AAV) is rare. The difficult diagnosis and treatment of this syndrome is described in this case report of the patient with SLE and severe kidney involvement resulting from AAV.

• Klíčová slova
• ANCA associated vasculitis, overlap syndrome, systemic lupus erythematosus.,
• MeSH
• ANCA-asociované vaskulitidy * komplikace   MeSH
• incidence MeSH
• lidé MeSH
• syndrom MeSH
• systémový lupus erythematodes * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Pulmonary syndrome is defined by occurrence of lung involvement (alveolar haemorrhage) in association with renal failure (with a typical crescentic necrotizing rapidly progressive glomerulonephritis). It is caused by an autoimmune disease, most frequently ANCA-associated vasculitides and anti-GBM (glomerular basement membrane) disease. Early establishment of the right diagnosis and immediate treatment are crucial for favourable prognosis of the patients. First choice therapy includes high-dose corticosteroids and cyclophosphamide, usually with plasma exchange added. Newer therapeutic possibilities include especially rituximab even though there is limited experience with its use in the settings of the most severe cases of pulmonary syndrome.

• Klíčová slova
• ANCA, anti‑glomerular basement membrane (anti‑GBM) antibodies, diffuse alveolar haemorrhage, rapidly progressive glomerulonephritis, rituximab, vasculitis,
• MeSH
• ANCA-asociované vaskulitidy * MeSH
• autoprotilátky MeSH
• glomerulonefritida * terapie   MeSH
• krvácení MeSH
• lidé MeSH
• syndrom MeSH
• výměna plazmy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH

Despite major advances in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) achieved in the last decades, a large proportion of AAV patients still develop end-stage renal disease. The survival of AAV patients dependent on dialysis is significantly worse compared with dialysis-independent AAV patients, but is comparable to other non-diabetic patients requiring dialysis. Renal transplantation (RTx) is the method of choice among renal replacement therapies and there has been increasing evidence that it is a suitable method with favorable patient- and graft-survival also in AAV patients. It is recommended to perform RTx after ≥12 months of remission, and ANCA positivity at the time of RTx is generally not considered a contraindication. Even though the risk of relapse after RTx is relatively low with current post-transplant immunosuppressive regimens, disease recurrence may occur. Besides cyclophosphamide, rituximab might become a therapeutic alternative for post-transplant AAV recurrence in the near future but its efficacy and safety in this setting needs to be confirmed in larger studies.

• Klíčová slova
• ANCA, outcome, relapse, renal transplantation, vasculitis,
• MeSH
• ANCA-asociované vaskulitidy komplikace   terapie   MeSH
• indukce remise MeSH
• lidé MeSH
• nemoci ledvin etiologie   chirurgie   MeSH
• přežívání štěpu MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

ANCA-associated vasculitis (AAV) is a potentially life-threatening disease with frequent and often severe kidney involvement which may result in end-stage renal disease. Anti-PR3 and anti-MPO disease are genetically distinct diseases and may have a different pathogenesis. Recent discovery of new autoantibodies (anti-LAMP-2) and the role of complement activation in the pathogenesis of AAV could result in better monitoring of the activity of the disease and identification of new treatment targets. The outcome of patients with AAV has dramatically improved, but long-term mortality still remains relatively high partly due to effective but relatively toxic immunosuppressive treatment. Recent studies demonstrated that B-cell depletion with rituximab is comparable to cyclophosphamide as induction treatment in newly diagnosed AAV patients and better than cyclophosphamide in relapsing patients. Rituximab-based maintenance treatment is superior to standard treatment with azathioprine. The use of more targeted treatment will hopefully be translated into a better long-term outcome of AAV patients.

• MeSH
• ANCA-asociované vaskulitidy komplikace   farmakoterapie   etiologie   mortalita   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• myší monoklonální protilátky terapeutické užití   MeSH
• nemoci ledvin etiologie   MeSH
• rituximab MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• myší monoklonální protilátky MeSH
• rituximab MeSH