- Klíčová slova
- lanadelumab, berotralstat,
- MeSH
- androgeny aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
- antagonisté bradykininových receptorů aplikace a dávkování farmakologie klasifikace terapeutické užití MeSH
- hereditární angioedémy * diagnóza farmakoterapie komplikace MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- kvalita života MeSH
- lidé MeSH
- plazmatický kalikrein antagonisté a inhibitory aplikace a dávkování farmakologie terapeutické užití MeSH
- premedikace klasifikace metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-γ production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases. OBJECTIVE: It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response. METHODS: CD4+ T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol in vitro for 60 h and analyzed by flow cytometry. IFN-γ and IL-10 levels in cell culture supernatants were measured using ELISA. RESULTS: CD4+ T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4+Tr1 cells from in vitro generated CD4+Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4+ T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-γ and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4+ T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4+ T cells produced less IFN-γ in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with αCD3/αCD46/IL-2/Calcitriol. CONCLUSION: Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Respiratory allergies mostly allergic rhinitis and asthma represent an important and increasing public health problem and one of the priorities for the European health systems. There is an increasing public concern regarding the persistence and severity of allergic diseases and many difficulties of health systems in providing prompt specialized medical assistance. Our study aims to highlight the main results of the Alliance 4Life project focused on the evaluation of the burden and management of respiratory allergies in primary care from Romania and comparative health-related data from four Central and Eastern European countries. METHOD: We developed a questionnaire focused on patients with allergic rhinitis and asthma directly addressed to general practitioner (GP) specialists from Romania who attended the annual national conference in Bucharest. RESULTS: The main results showed that patients with respiratory allergies are frequently encountered in primary care practice, only a few patients are evaluated by allergists and there is a clear need for education in this field. CONCLUSIONS: This preliminary study confirms that respiratory allergies represent a considerable burden in primary care and the questionnaire may be a useful tool in further studies considering the experience of other healthcare systems. More advanced studies integrating epidemiology with data on air pollution and environmental conditions should be envisaged.
- MeSH
- alergická rýma terapie epidemiologie MeSH
- bronchiální astma terapie epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- osobní újma zaviněná nemocí MeSH
- primární zdravotní péče * MeSH
- průzkumy a dotazníky MeSH
- respirační alergie epidemiologie terapie diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Bulharsko MeSH
- Česká republika MeSH
- Polsko MeSH
- Rumunsko MeSH
Primární protilátkové deficience (PAD) jsou charakterizované porušenou tvorbou protilátek se snížením jednoho nebo více izotypů, případně porušenou tvorbou specifických protilátek. Klinickému obrazu dominují recidivující, převážně sinopulmonální infekce nejčastěji vyvolané opouzdřenými bakteriemi. V různé míře se přidružují projevy imunitní dysregulace (autoimunitní, granulomatózní nebo lymfoproliferativní) nebo maligní onemocnění. Plicní postižení se vyskytuje zejména u pacientů s běžnou variabilní imunodeficiencí (CVID), X-vázanou aga-maglobulinemií (XLA) a autozomálně recesivně dědičnými hyper IgM syndromy (HIGM). Typickým nálezem jsou bronchiektázie, které jsou přímým důsledkem opakovaných infekcí. Intersticiální plicní procesy jsou naopak spíše projevem dysregulace imunitní odpovědi. Specifickou jednotkou ze skupiny intersticiálních plicních procesů je granulomatózně-lymfocytární intersticiální plicní nemoc (GLILD), kterou nalézáme zejména u pacientů s CVID a která se vyznačuje závažnou prognózou. Základním terapeutickým přístupem u protilátkových deficitů je imu-noglobulinová substituce, další léčebné postupy závisí na typu komplikace. V péči o pacienty s primárními protilátkovými imunodeficity hraje ústřední roli klinický imunolog ve spolupráci s ostatními odbornostmi, a to zejména pneumology.
Primary antibody deficiencies (PAD) are characterized by impaired antibody production which leads to decreased serum levels of one or more isotypes or impaired production of specific antibodies. Recurrent sinopulmonary infections caused by encapsulated bacteria are the main clinical manifestation. Immune dysregulation (autoimmunity, granuloma or lymphoproliferation) and malignancy are also common in these diseases. Lung impairment is typical for patients with common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA) and autosomal-recessive hyper-IgM syndromes (HIGM). Bronchiectasis as a result of recurrent infections is a common finding in those patients. On the contrary, interstitial lung disease is a manifestation of immune dysregulation. Some patients with CVID suffer from granulomatous-lymphocytic interstitial lung disease (GLILD) which is a specific type of interstitial lung diseases, and which is associated with poor prognosis. Immunoglobulin replacement is the main therapeutic approach in patients with antibody deficiencies. Other therapeutic strategies depend on the type of complications. The key role in management of patients with PAD plays clinical immunologist in collaboration with other physicians, especially with pneumologists.
