The presence of a broad spectrum of autoantibodies in Sjögren's syndrome (SjS) patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren's syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF. and J. Krejsek, M. Koláčková, I. Lindrová, R. Slezák, C. Andrýs
Objective: A prospective study was performed to determine the relation between plasma N-terminal pro brain natriuretic peptide (NT-proBNP) levels and short- and long-term mortality in patients with acute heart failure (AHF). Settings: 1st Department of Medicine, Institute of Clinical Biochemistry and Diagnostics, Institute of Clinical Immunology and Allergology, Charles University Prague, Medical Faculty and Faculty Hospital Hradec Králové. Methods: NT-proBNP levels were measured at time of admission in 92 consecutive patients with AHF. Results: During one-year follow-up, 32 patients died. Mean levels of NT-proBNP were signifi cantly lower among the survivors (NT-proBNP: 7 855.4 ± 9 919.9 ng/l, vs.15 470.6 ± 11 273.1, p < 0.001). Hazard ratio (HR) for death from any cause for the patients with NT-proBNP levels above median as compared with those with NT-proBNP below median was 2.91 (0.84–10.10) for 7-day, 3.58 (1.17–11.1) for 28-day, and 3.76 (1.49–9.55): for 1-year mortality. Conclusions: NT-proBNP levels are elevated in acute heart failure, NT-proBNP is also the marker of short- and long-term mortality in acute decompensated heart failure patients, and provides prognostic information above and beyond that provided by conventional cardiovascular risk factors., Cíl studie: Posoudit vztah mezi plazmatickou hladinou N-terminálního mozkového natriuretického peptidu (NT-proBNP) a parametry krátko- i dlouhodobé mortality pacientů s akutním srdečním selháním. Název a sídlo pracoviště: 1. interní klinika, Ústav klinické biochemie a diagnostiky, Ústav imunologie a alergologie, Lékařská fakulta Univerzity Karlovy a Fakultní nemocnice, Hradec Králové. Materiál a metody: V souboru 92 pacientů s akutním srdečním selháním byla změřena hladina NT-proBNP ze vzorku krve odebraného v době přijetí. Parametry krátko- i dlouhodobé mortality byly stanoveny z dat z následného jednoročního sledování vyšetřovaného souboru. Výsledky: V průběhu sledování klinického stavu do konce prvního roku 32 pacientů zemřelo. Průměrná hladina NT-proBNP byla u přeživších pacientů významně nižší (NT-proBNP: 7 855,4 ± 9 919,9 ng/l, vs 15 470,6 ± 11 273,1, p < 0,001). Hazard ratio (HR) pro úmrtí z jakékoliv příčiny u pacientů nad medián bylo 2,91 (0,84–10,10) pro 7denní, 3,58 (1,17–11,1) pro 28denní a 3,76 (1,49–9,55) pro jednoroční mortalitu. Závěr: Hladina NT-proBNP je významně zvýšena u pacientů s akutním srdečním selháním. Analýza ukázala, že hladiny NT-proBNP jsou u pacientů s akutním srdečním selháním ukazatelem krátko- i dlouhodobé mortality., Pudil Radek, Tichý M., Andrýs C., Bláha V., Vojáček J., and Lit.: 22
Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T -cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT ). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT , as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001)., Kateřina Kondělková, Doris Vokurková, Jan Krejsek, Lenka Borská, Zdeněk Fiala, Květa Hamáková, Ctirad Andrýs, and Literatura 39
Introduction: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. Aim: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. Methods: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. Results: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). Conclusion: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated. and M. Tošovský, P. Bradna, C. Andrýs, K. Andrýsová, E. Čermáková, T. Soukup
Cardiac surgery is inseparably linked to the activation of innate immunity cells recognizing danger signals of both endogenous and exogenous origin via pattern recognition receptors such as TLR receptors. Therefore, we followed by flow cytometry TLR2 and TLR4 expression on blood monocytes and granulocytes of patients who underwent coronary artery bypass grafting using beating heart surgery (off-pump, n = 34), with use of standard cardiopulmonary bypass (CPB), (on-pump, n = 30), and miniinvasive CPB (mini on-pump, n = 25), respectively, before, during surgery, and up to 7th postoperative day. TLR2 and TLR4 expression both on monocytes and granulocytes was significantly diminished already at the end of CPB being highly significantly decreased at the end of surgery in all patients' groups. TLR2 and TLR4 expression reached preoperative value at the 1st postoperative day being significantly higher at the 3rd postoperative day. Using intracellular staining we found the peak of TLR2 and TLR4 expression inside of monocytes and granulocytes at the first postoperative day in a subgroup of on-pump patients. In conclusion, TLR2 and TLR4 expression is significantly modulated in patients undergoing coronary artery bypass grafting as a part of adaptive homeostatic mechanisms induced by major surgery. The very surgical trauma is responsible for TLR2 and TLR4 modulation. Surprisingly, cardiopulmonary bypass itself was little contributing to the modulation of TLR2 and TLR4 expression. and J. Krejsek, M. Kolácková, J. Mand'ák, P. Kunes, Z. Holubcová, D. Holmannová, M. AbuAttieh, C. Andrýs