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.
- Klíčová slova
- Immune thrombocytopenia, antiplatelet autoantibodies, immunoregulatory index, lymphocyte subpopulations,
- 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
- Názvy látek
- autoprotilátky 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.
- Klíčová slova
- Hypogammaglobulinemia, Immunogenicity, SARS-CoV-2, Spikevax, Vaccination,
- 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
- Názvy látek
- imunoglobulin A MeSH
- imunoglobulin G MeSH
- messenger RNA MeSH
- vakcíny proti COVID-19 * 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.
- Klíčová slova
- CD-64, CRP, TLR-2, malignant pleural effusion, talc, thoracoscopy,
- MeSH
- C-reaktivní protein metabolismus MeSH
- délka pobytu MeSH
- leukocyty fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom komplikace MeSH
- maligní mezoteliom 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
- Názvy látek
- C-reaktivní protein MeSH
- mastek 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
- Názvy látek
- antigeny diferenciační myelomonocytární MeSH
- biologické markery MeSH
- CD antigeny MeSH
- CD163 Antigen MeSH
- mastek MeSH
- receptory buněčného povrchu MeSH
- TLR2 protein, human MeSH Prohlížeč
- toll-like receptor 2 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
- Názvy látek
- mastek MeSH
- TLR2 protein, human MeSH Prohlížeč
- toll-like receptor 2 MeSH
AIMS: Coronary artery bypass grafting (CABG) is linked to the induction of the blood coagulation/fibrinolysis cascade, which is an integral component of inflammation induced by cardiac surgery. We followed the modulation of urokinase plasminogen activator receptor uPAR (CD87) separately for monocytes and granulocytes in blood of cardiac surgery patients. METHODS: Expression of uPAR, analyzed as Median Fluorescence Intensity (MFI), on blood monocytes and granulocytes was determined by flow cytometry. Changes in uPAR expression in patients undergoing CABG using standard cardiopulmonary bypass ("on-pump") were compared to the changes in uPAR expression in patients undergoing CABG using mini-invasive cardiopulmonary bypass ("mini on-pump"). RESULTS: In "on-pump" patients, the median of uPAR expression on granulocytes before surgery was 18.1 (InterQuartile Range (IQR): 15.6-20.4). uPAR expression was significantly decreased after surgery (p<0.001), on the first postoperative day (p<0.001), and on the third postoperative day (p<0.05). In "mini on-pump" patients, the median of uPAR expression on granulocytes before surgery was 15.2 (IRQ: 13.8-19.4). The significantly decreased uPAR expression was found only at the end of surgery (p<0.05). The similar pattern of uPAR expression was also found for monocytes. The preoperative level in "on-pump" patients was 23.3 (IRQ: 18.9-30.2). There was significantly decreased uPAR expression at the end of surgery (p<0.01) and at the first postoperative day (p<0.05). In "mini on-pump" patients, the preoperative uPAR expression was 16.9 (IQR: 14.5-20.2). Expression of uPAR was significantly decreased only after surgery (p<0.05). When comparing "onpump" patients to "mini on-pump" patients, no significant differences in the expression of uPAR were found. CONCLUSION: uPAR expression on granulocytes and monocytes is significantly modulated by cardiac surgery.
- MeSH
- granulocyty imunologie MeSH
- koronární bypass * MeSH
- lidé středního věku MeSH
- lidé MeSH
- monocyty imunologie MeSH
- receptory urokinázového aktivátoru plazminogenu imunologie MeSH
- senioři 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
- Názvy látek
- receptory urokinázového aktivátoru plazminogenu MeSH
AIMS: Cardiac surgical operation is inseparably linked to the induction of an inflammatory response. Both humoral and cellular regulatory mechanisms are operating to maintain body homeostasis. We followed the changes in the expression of CD200/CD200R regulatory molecules on monocytes and granulocyte of cardiac surgical patients operated on using either standard (OP) or modified "mini-invasive" cardiopulmonary bypass (MOP). METHODS: Expression of CD200/CD200R regulatory molecules was determined by flow cytometry. RESULTS: The expression of CD200R on granulocytes was increased after surgery in both groups of patients, but the increase was statistically significant only in OP patients (p<0.01). At this time point, there was a significant difference in CD200R expression on granulocytes when comparing OP to MOP patients, being higher in the former group (p<0.01). The expression of CD200R on monocytes was diminished after surgery and during an early postoperative period in both groups of patients. The expression of CD200 on monocytes was significantly diminished after surgery in both groups (p<0.01). Nonetheless, we observed an increase in CD200 expression in OP patients at the 3rd postoperative day. There was a statistically significantly increased CD200 expression on monocytes of OP patients (p<0.001) at the 3rd postoperative day when we compared OP and MOP groups. The expression of CD200 on granulocytes was significantly higher after surgery and at the 3rd postoperative day in OP when compared to MOP patients. CONCLUSIONS: CD200R expression on granulocytes was significantly increased, while CD200 and CD200R expression on monocytes was decreased after cardiac surgery.
- MeSH
- antigeny povrchové imunologie MeSH
- CD antigeny imunologie MeSH
- granulocyty imunologie MeSH
- kardiochirurgické výkony škodlivé účinky MeSH
- kardiopulmonální bypass MeSH
- lidé středního věku MeSH
- lidé MeSH
- monocyty imunologie MeSH
- orexinové receptory MeSH
- průtoková cytometrie MeSH
- receptory buněčného povrchu imunologie MeSH
- senioři MeSH
- zánět etiologie imunologie 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
- Názvy látek
- antigens, CD200 MeSH Prohlížeč
- antigeny povrchové MeSH
- CD antigeny MeSH
- CD200R1 protein, human MeSH Prohlížeč
- orexinové receptory MeSH
- receptory buněčného povrchu MeSH
INTRODUCTION: It is widely accepted that expression of ZAP-70 in chronic lymphocytic leukemia (CLL) remains stable in time. However, data supporting this notion are surprisingly scarce. Therefore, we assessed expression of ZAP-70 in serial samples taken during the course of the disease. PATIENTS AND METHODS: We studied 44 patients with CLL diagnosed according to NCI-WG criteria (34 men, 10 women, median age 62, range, 36-81). A total of 104 samples were examined; all patients had at least two measurements. Median interval between the first and the second sample was 13 months (range, 2-36). ZAP-70 expression was detected by flow cytometry using phycoerythrin-conjugated monoclonal antibody clone 1E7.2 and negative isotype control. Twenty percent of positive cells were considered as the threshold of positivity. RESULTS: Significant change in ZAP-70 expression (i.e. from positivity to negativity and vice versa) was detected in 15/44 patients (34%). Interestingly, 7/8 patients whose ZAP-70 expression converted to positivity had unmutated IgVH genes. In addition, the conversion was accompanied by clinical progression or relapse in all but one patient. On the other hand, 5/7 patients with loss of ZAP-70 had stable clinical course. One patient became ZAP-70-negative during treatment with prednisone for autoimmune hemolytic anemia. CONCLUSIONS: In contrast to commonly accepted opinion, significant change in ZAP-70 expression in time was detected in a substantial proportion of our patients with CLL. While the conversion to ZAP-70 negativity was found predominantly in patients with stable disease, change to positivity was typical in patients with unmutated IgVH genes at the time of progression or relapse. Based on our pilot results, repeated assessment of ZAP-70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP-70-negative.
- MeSH
- chronická lymfatická leukemie enzymologie etiologie MeSH
- dospělí MeSH
- geny pro těžké řetězce imunoglobulinů MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery krev MeSH
- pilotní projekty MeSH
- progrese nemoci MeSH
- protein-tyrosinkináza ZAP-70 krev MeSH
- recidiva MeSH
- senioři nad 80 let MeSH
- senioři 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
- nádorové biomarkery MeSH
- protein-tyrosinkináza ZAP-70 MeSH
- ZAP70 protein, human MeSH Prohlížeč
BACKGROUND: Cardiac surgery provokes a systemic inflammatory response in any patient. This complex body reaction involves also RANK/RANKL molecules which have been recently identified as principal regulators of bone metabolism. AIMS: To follow the changes in the expression of RANK/RANKL molecules on innate immune cells of cardiac surgical patients. PATIENTS AND METHODS: Twenty-six patients undergoing cardiac surgical were assigned to undergo coronary artery bypass grafting using either cardiopulmonary bypass ("on-pump") or modified "miniinvasive on-pump". The expression of RANK/RANKL was performed by flow cytometry. RESULTS: Significantly increased expression of RANK on monocytes of "miniinvasive on-pump" patients was found at the 1st, the 3nd, and 7th postoperative days. The similar pattern was found also for monocyte RANKL expression. In addition, RANKL expression was significantly increased at the 3rd postoperative day in "on-pump" patient. No significant differences between "miniinvasive on-pump" and "on-pump" cardiac surgical patients were found. CONCLUSION: The expression of both RANK and RANKL molecules is significantly enhanced on monocytes of "miniinvasive on-pump" cardiac surgical patients.
- MeSH
- granulocyty metabolismus MeSH
- kardiopulmonální bypass MeSH
- koronární bypass * MeSH
- lidé MeSH
- ligand RANK metabolismus MeSH
- monocyty metabolismus MeSH
- protein RANK metabolismus MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ligand RANK MeSH
- protein RANK MeSH
BACKGROUND: The scavenger receptor for complexes hemoglobin-haptoglobin (CD163), which is expressed on monocytes/ macrophages, is shed to the body fluids in a soluble form (sCD163). OBJECTIVES: To evaluate the dynamics of sCD163 in the blood of patients undergoing cardiac surgery. PATIENTS AND METHODS: Sixty-one adult patients who underwent coronary artery bypass grafting (CABG) were enrolled in the study. They were assigned to undergo CABG using either cardiopulmonary bypass (CPB), "on-pump", (22 patients), modified CPB, mini "on-pump", (17 patients) or without CPB, "off-pump", (22 patients) surgery. Serum levels of sCD163 in venous blood samples taken before and after surgery, and during an early postoperative period, were evaluated by Macro 163(TM) diagnostic kit (IQ Products, Groningen, NL). RESULTS: Compared to the preoperative levels ("on-pump"; 344 ng/mL, "off-pump"; 314.5 ng/mL, mini-invasive "on-pump"; 336.5 ng/mL) serum levels were elevated at the finish of surgery, reaching maximum at the 1(st) postoperative day ("onpump"; 658 ng/mL; p<0.05, "off-pump"; 810.5 ng/mL; p<0.01; mini-invasive "on-pump"; 663 ng/mL; non-significant).No significant differences regarding the serum levels of sCD163 between different surgical approaches were found. CONCLUSION: Serum level of sCD163 scavenger molecule for hemoglobin is elevated at the end of surgery and at the 1(st) postoperative day, being little influenced by cardiopulmonary bypass.
- MeSH
- antigeny diferenciační myelomonocytární krev MeSH
- CD antigeny krev MeSH
- haptoglobiny metabolismus MeSH
- hemoglobiny metabolismus MeSH
- kardiopulmonální bypass škodlivé účinky MeSH
- koronární bypass škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory buněčného povrchu krev MeSH
- senioři MeSH
- zánět krev etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny diferenciační myelomonocytární MeSH
- CD antigeny MeSH
- CD163 Antigen MeSH
- haptoglobin-hemoglobin complex MeSH Prohlížeč
- haptoglobiny MeSH
- hemoglobiny MeSH
- receptory buněčného povrchu MeSH