OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and altered production. Despite the well-described pathophysiological background of immune dysregulation, current treatment guidelines consist of monotherapy with different drugs, with no tool to predict which patient is more suitable for each therapeutic modality. METHODS: In our study, we attempted to determine differences in the immune setting, comparing the patients' responses to administered therapy. During 12-month follow-up, we assessed blood count, antiplatelet autoantibodies, and T lymphocyte subsets in peripheral blood in 35 patients with ITP (newly diagnosed or relapsed disease). RESULTS: Our data show that the value of antiplatelet autoantibodies, the percentage of cytotoxic T lymphocytes, and the immunoregulatory index (IRI, CD4+ / CD8+ T cell ratio) differ significantly by treatment response. Responders have a higher IRI (median 2.1 vs. 1.5 in non-responders, P = 0.04), higher antiplatelet autoantibodies (median 58 vs. 20% in non-responders, P = 0.01) and lower relative CD8+ T cells count (P = 0.02) before treatment. DISCUSSION: The results suggest that immunological parameters (antiplatelet autoantibodies, relative CD8+ T cell count and IRI) could be used as prognostic tools for a worse clinical outcome in patients with ITP. CONCLUSION: These biomarkers could be utilized for stratification and eventually selection of treatment preferring combination therapy.
- MeSH
- autoprotilátky MeSH
- CD8-pozitivní T-lymfocyty MeSH
- idiopatická trombocytopenická purpura * diagnóza farmakoterapie MeSH
- lidé MeSH
- lymfocyty MeSH
- trombocytopenie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency. METHODS: We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay). RESULTS: We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination. CONCLUSION: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.
- MeSH
- běžná variabilní imunodeficience * terapie MeSH
- COVID-19 * prevence a kontrola MeSH
- imunoglobulin A MeSH
- imunoglobulin G MeSH
- lidé MeSH
- messenger RNA MeSH
- SARS-CoV-2 MeSH
- syndromy imunologické nedostatečnosti * MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: One option for the palliative treatment of recurrent malignant pleural effusion is powdered talc using thoracoscopy. This paper presents the results of selected systemic and local manifestations of the talc-induced inflammatory reaction using a videothoracoscope. METHOD: A total of 114 patients with repeated malignant pleural effusion were treated at the Cardiac Surgery Clinic in Hradec Kralove from January 2010 to December 2012. Those with a life expectancy more than ≥ 3 months were eligible for talcage surgery. The group was retrospectively divided according to treatment results into Group A (N1 = 98 - successful) and Group B (N2 = 16 - relapsing). The pleural effusion was quantified using ultrasound over 1 year at 3-month intervals. Systemic changes due to the inflammatory reaction (body temperature, serum leukocyte and CRP levels) were evaluated. Local indicators of inflammation included changes in the leukocyte cell population in the effusion and changes in the pleural CRP levels. The dynamics of local expression of membrane receptors TLR-2 and CD-64 on granulocyte and monocyte cell populations in the pleural effusion were also evaluated. RESULTS: The reaction after talcage, included a significant increase in axillary temperature and leukocyte count, 12 h after the procedure. The dynamics were different in the two groups. The dynamics of local inflammatory changes were an early increase in the pleural CRP levels in both groups. The time interval of local inflammatory development and duration was related to the treatment efficacy and showed a significant rise 2 h after talcage in Group A. In Group B the local inflammatory reaction was slower and the rise was only observed 24 h after talc application. A decrease in lymphocyte count and an increase in granulocyte count 2 h after talcage were found. After an initial drop in monocyte level, a rise occurred within 24 h after talcage. Changes in the expression of TLR-2 and CD-64 receptors in relation to their cell carriers were observed depending on time after talcage. CONCLUSION: The differences in the serum and pleural effusion CRP levels suggest that the surgical stress manifests itself locally in the pleural space with a lower intensity and time delay. The TLR-2 and CD-64 receptors exhibit different behaviour depending on the type of cell membrane where they are found. The inverse relation between the granulocyte increase and TLR-2 receptor decrease in the membrane immediately after talcage is a new finding. The dynamics of TLR-2 expression on the monocytes demonstrates a direct proportion between the increasing expression of the TLR-2 receptor and increasing percent fraction of the cell carrier.
- MeSH
- C-reaktivní protein metabolismus MeSH
- délka pobytu MeSH
- leukocyty fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom komplikace MeSH
- maligní pleurální výpotek diagnostické zobrazování etiologie terapie MeSH
- mastek aplikace a dávkování škodlivé účinky MeSH
- metastázy nádorů MeSH
- mezoteliom komplikace MeSH
- nádory plic komplikace MeSH
- paliativní péče metody MeSH
- pleuritida chemicky indukované MeSH
- pleurodéza škodlivé účinky metody MeSH
- prediktivní hodnota testů MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tělesná teplota fyziologie MeSH
- torakoskopie metody MeSH
- ultrasonografie MeSH
- výsledek terapie 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
- MeSH
- antigeny diferenciační myelomonocytární metabolismus MeSH
- biologické markery MeSH
- CD antigeny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek * metabolismus terapie MeSH
- mastek terapeutické užití MeSH
- membránové glykoproteiny metabolismus MeSH
- neúspěšná terapie MeSH
- pleurodéza MeSH
- prognóza MeSH
- receptor TREM-1 MeSH
- receptory buněčného povrchu metabolismus MeSH
- receptory imunologické metabolismus MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- toll-like receptor 2 metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Kontinuální tvorba výpotků jakékoliv etiologie zásadním způsobem ovlivňuje kvalitu života nemocných. Akumulace tekutiny v pleurální dutině postupně komprimuje plicní parenchym. Prvním příznakem bývá progrese námahové dušnosti, později se přidává i klidová dušnost. S nárůstem výpotku dochází ke kompresi plicního parenchymu s rozvojem plicní atelektázy. Nemocný je ohrožen vznikem zánětového onemocnění plic v nevzdušném plicním parenchymu. U diagnózy maligního onemocnění je riziko zánětových komplikací výrazně vyšší vzhledem k předchozí chemoterapii či radioterapii, která zásadním způsobem snižuje imunitu. Opakovaná tvorba výpotku se výrazně podílí na rozvoji terminálního stavu nádorové kachexie. Efektivní metodou léčby je chemická pleurodéza, která se užívá u vybraného spektra nemocných. Principem je navození aseptické pleuritidy. Nejefektivnější cestou aplikace léčiva je videotorakoskopie. V souboru bylo 47 nemocných, 29 (61,7 %) mužů a 18 (38,3 %) žen, s cytologicky prokázaným recidivujícím maligním pleurálním výpotkem. Věkové rozmezí 42–80 let, Ø věk 65 let. Cílem práce bylo objektivizovat průběh celkových a lokálních zánětových změn po talkáži. Efekt léčby nebyl ovlivněn základním typem nádorového onemocnění. U obou skupin nebyly významně odlišné pooperační komplikace, což dokládá bezpečnost zvolené metody a podporuje správně zvolený algoritmus léčby.
Continuous pleural effusion production of any aetiology can significantly affect the quality of patients life. Chronic effusion accumulation in the pleural cavity can lead to lung parenchyma compression. The first symptom of this entity is a progressive exertional dyspnea, which can later turn in dyspnea at rest. With the increase of the pleural effusion volume, pulmonary atelectasis can develop due to chronic parenchycha compression. The patient is at risk of inflamatory complications from the territory of non-ventilated parenchyma. Patients with a diagnosis of malignant disease have this risk considerably higher due to their previous chemotherapy or radiation, which substantially affect the immunity system. Repeated pleural effusion formation can significantly take part in the development of the terminal status of cancer cachexia. An effective method of palliative treatment is a chemical pleurodesis, which is used in selected patients. The principle is inducing aseptic inflammation. The most effective way of application is via videothoracoscopy. In a group of 47 patients, there were 29 (61.7 %) men and 18 (38.3 %) women with cytologically diagnosed recurrent malignant pleural. The age ranged between 42 and 80 with average age of 65 years. The aim was to assess the course of local and systemic inflammatory changes after talc application. The effect of treatment was not influenced by the type of malignancy . In both groups there was no significant difference in postoperative complications. This proves the safety of the selected procedure and also supports the correctness of the chosen algorithm of treatment.
- Klíčová slova
- sCD-163, talkáž,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek * etiologie farmakoterapie chirurgie MeSH
- mastek terapeutické užití MeSH
- pleurodéza * metody statistika a číselné údaje MeSH
- senioři MeSH
- torakoskopie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H₂Mg₃(SiO₃)₄) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. METHODS: The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. RESULTS: Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in pleural fluid before the talc poudrage. This showed limited ability to create an adequate inflammatory response to external stimuli. This group also showed lower levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect of the treatment was not influenced by morphologic tumour type. No statistically significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. CONCLUSIONS: There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.
- MeSH
- antigeny diferenciační myelomonocytární analýza MeSH
- biologické markery analýza MeSH
- CD antigeny analýza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek imunologie terapie MeSH
- mastek imunologie terapeutické užití MeSH
- pleurodéza * MeSH
- receptory buněčného povrchu analýza MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- toll-like receptor 2 analýza 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
The aim of this study was to examine the role of TLR2 molecule in pleural space during thoracoscopic talc pleurodesis period in patients with malignant pleural effusion. We analyzed TLR2 molecule in soluble form as well as on membrane of granulocytes in pleural fluid. Pleural fluid examination was done at three intervals during pleurodesis procedure: 1st-before the thoracoscopic procedure, 2nd-2 hours after the terminating thoracoscopic procedure with talc insufflation, 3rd-24 hours after the thoracoscopic procedure. We reported significant increase of soluble TLR2 molecule in pleural fluid effusion during talc pleurodesis from preoperative value. This increase was approximately 8-fold in the interval of 24 hours. The changes on granulocyte population were quite different. The mean fluorescent intensity of membrane TLR2 molecule examined by flow cytometry on granulocyte population significantly decreased after talc exposure with comparison to prethoracoscopic density. To estimate the prognostic value of TLR2 expression in pleural fluid patients were retrospectively classified into either prognostically favourable or unfavourable groups. Our results proved that patients with favourable prognosis had more than 3-fold higher soluble TLR2 level in pleural fluid early, 2 hours after talc pleurodesis intervention.
- MeSH
- granulocyty účinky léků metabolismus MeSH
- insuflace metody MeSH
- lidé MeSH
- maligní pleurální výpotek metabolismus terapie MeSH
- mastek aplikace a dávkování MeSH
- pleura účinky léků metabolismus MeSH
- pleurodéza metody MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- toll-like receptor 2 metabolismus MeSH
- torakoskopie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Imunitní systém je v kooperaci s neuroendokrinní soustavou odpovědný za udržování homeostázy. Podněty, které vedou k narušení homeostázy, jsou označovány jako nebezpečné. Tělo je identifikuje prostřednictvím receptorů PRR s následnou zánětovou odpovědí. Buňky vrozené imunity (dendritické buňky) zpracovávají nebezpečné vzory a z nich vzniklé antigenní fragmenty navázané na molekuly HLA-I, II předkládají T lymfocytům. T lymfocyty proliferují a vykazují efektorové funkce. Zánětová odpověď je na řadě úrovní regulována tak, aby imunitní odpověď byla realizována efektivně s minimálními negativními dopady na organizmus.
The immune system, together with the neuroendocrine system, is responsible for the maintenance of homeostasis. Signals which disturb homeostasis are recognized as danger signals by PRR receptors with subsequent development of the inflammatory response. Innate immunity cells (dendritic cells) process danger molecules. Antigenic fragments from danger molecules are presented to T cells in the context of HLA-I,II molecules. T cells proliferate following antigenic stimulation, displaying numerous effector and regulatory functions. The inflammatory response is carefully regulated on numerous levels to achieve protective immunity without harmful effects on the organism.
- Klíčová slova
- imunitní odpověď, regulace,
- MeSH
- cytokiny krev MeSH
- financování organizované MeSH
- imunitní systém - jevy fyziologie imunologie MeSH
- lidé MeSH
- receptory rozpoznávající vzory imunologie MeSH
- regulační T-lymfocyty imunologie MeSH
- zánět imunologie krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH