Cross-disease innate gene signature: Emerging diversity and abundance in RA comparing to SLE and SSc

Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (n=36, DAS28 >= 3.2), SLE (n=28, SLEDAI>6), and SSc (n=22, revisedEUSTARindex>2.25). Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (Pcorr<0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (Pcorr<0.02). Applying the association rule analysis, six rules (combinations and expression of genes describing disease) were identified for RA (most frequently included high TLR3 and/or IL1RAP/IL1R3) and three rules for SLE (low IL1RN and IL18R1) and SSc (low TLR5 and IL18R1). This first cross-disease study identified emerging heterogeneity in the innate signature of RA patients with many upregulated innate genes compared to that of SLE and SSc.Web of Science2019art. no. 357580

Motor-functional preparation of tennis players during pre-season in South Bohemia region and Pilsen region

Bakalářská práce je zaměřena v písemné části na motoricko-funkční přípravu tenistů-starších žáků, kde je má pozornost věnována hlavně charakteristice kondiční přípravy v předzávodním období. Dále se zabývám v této části pohybovými dovednostmi a motorickými schopnostmi v tenise. Cílem praktické části práce je vytvoření fotodokumentace s výběrem vhodných cvičení z pohybových dovedností v tenise a získání informací z motoricko-funkční přípravy tenistů v předzávodním období u starších žáků v Plzeňském a Jihočeském kraji pomocí dotazníkového šetření.ObhájenoThis thesis is in its written part focused on the theme of motor funcional preparation of tennis players older pupils. In this part my attention is concentrated on the characteristic of condition training in the pre race period. In this part I also deal with the issue of motion and motor skills in tennis. The main aim of the practical part of this thesis is to produce a collection of photographs showing the suitable exercises to gain motor skills in tennis. The second aim is to obtain information about motor functional preparation of tennis players (older pupils) in pre race period in Pilsen and South Bohemian region

Cardiovascular events in patients with systemic lupus erythematosus

AbstractIntroductionCardiovascular involvement represents the leading cause of mortality in SLE patients. Its most common manifestations include pericarditis, valvular affections, conduction disorders, and arterial hypertension. Pulmonary hypertension and coronary arteritis are seen less often. Venous thrombosis directly related to SLE affects about 10% of SLE cases. Acceleration of atherosclerosis is very important and so are the ensuing cardiocerebral events, the most common of these being myocardial infarctions (MIs), cerebrovascular events, thromboembolic events (TEs), heart failure, and sudden death. We analyzed the frequency of cardiovascular events and their relationship to selected risk factors in a cohort of SLE patients followed in a single clinical center.MethodsThe studied population comprised 63 SLE patients (women: men=53: 10, mean age 38.4±12.7 years, mean disease duration 143±82 months, BMI 24.74±5.06, waist circumference 83.38±16.58cm), including 25 patients with lupus nephritis. Intima-media thickness (IMT) was assessed ultrasonographically in a standard manner. Of laboratory values, serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), anti-ds-DNA, antinucleosomal antibodies (ANUC), complement components C3 and C4, and ENA antibodies were measured. Clinical disease activity was assessed using indices of activity and cumulative damage such as SLEDAI and SLICC. Screening for traditional cardiovascular risk factors was based on appropriate questionnaires. Detailed analysis was employed to calculate cumulative doses of glucocorticoids and other immunosuppressants and to evaluate the use of anticoagulants, antiaggregants, statins, and ACE inhibitors.ResultsA total of 21 (33%) patients had a history of cardiovascular event during the course of their SLE: there were 3 myocardial infarctions (4.7% of the entire population, 14% of all cardiovascular events), 8 cerebrovascular events (12.7%, resp. 38%), and 12 thromboembolic events (19%, resp. 57%). In two patients, two different manifestations of cardiovascular involvement were combined – cerebrovascular event and MI in one, cerebrovascular event and TE event in the other. Cardiovascular events correlated with obesity, waist and hip circumference, smoking, total cholesterol, LDL, TC/HDL ratio, and apolipoproteins A-1 and B.Borderline statistical significance was noted for disease activity, hsCRP, positivity of RNP and anticardiolipin antibodies, lupus anticoagulant (p=0.06) and intima-media thickness (p=0.07). Subgroups of patients with cardiovascular event and arterial hypertension were also analyzed in more detail.ConclusionIn this article, we point to the high rate of cardiovascular events in SLE patients, thus confirming the need to pay appropriate attention to cardiovascular problems in the field of rheumatology

Modulatory effect of the Euro-Lupus low-dose intravenous cyclophosphamide regimen on circulating immune cells in systemic lupus erythematosus

A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ manifestations of systemic lupus erythematosus (SLE), particularly lupus nephritis (LN). There are no data on the distributions and dynamics of immune cell populations in patients with various treatment outcomes. The circulating immune cells of 11 female SLE patients were assessed before and after Euro-Lupus regimen (cumulative dose of 3000 mg CFA) by flow cytometry together with those of 16 healthy women. A subanalysis was performed in LN patients who achieved complete remission (CR; n = 3), partial remission (PR; n = 4), and no response (NR; n = 2). In SLE, the Euro-Lupus regimen decreased the percentage and absolute count of B cells; increased the percentage of CD8(+) T cells, T regulatory cells, neutrophils, and monocyte subsets; and activated T and NK cells compared to healthy controls (P < 0.050). Patients with LN achieving CR had significantly lower proportions of CD27(+) B memory cells compared to poor responders (PR/NR, P = 0.035). The post-treatment percentages and absolute numbers of B cells, T cells, NK cells, monocytes, and neutrophils showed high inter-individual variability with no association with treatment outcome. Our pilot study revealed the dynamics of changes in immune cell populations in SLE patients during a Euro-Lupus regimen, mainly the lowering of B cells. In LN patients who achieved CR, a lower proportion of CD27(+) B memory cells was evident compared to poor responders (PR/NR). Further studies on usefulness of monitoring immune cells for treatment response prediction on larger cohorts are needed.Web of Science67642541

Revealed heterogeneity in rheumatoid arthritis based on multivariate innate signature analysis

Objective A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA. Methods The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/ IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28 >= 3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55). Results Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity- related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity. Conclusion Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.Web of Science38229828

Revealed heterogeneity in rheumatoid arthritis based on multivariate innate signature analysis

Objective A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA. Methods The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/ IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28 >= 3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55). Results Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity- related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity. Conclusion Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.Web of Science38229828

To ventilate or not to ventilate during bystander CPR — A EuReCa TWO analysis

Background: Survival after out-of-hospital cardiac arrest (OHCA) is still low. For every minute without resuscitation the likelihood of survival decreases. One critical step is initiation of immediate, high quality cardiopulmonary resuscitation (CPR). The aim of this subgroup analysis of data collected for the European Registry of Cardiac Arrest Study number 2 (EuReCa TWO) was to investigate the association between OHCA survival and two types of bystander CPR namely: chest compression only CPR (CConly) and CPR with chest compressions and ventilations (FullCPR). Method: In this subgroup analysis of EuReCa TWO, all patients who received bystander CPR were included. Outcomes were return of spontaneous circulation and survival to 30-days or hospital discharge. A multilevel binary logistic regression analysis with survival as the dependent variable was performed. Results: A total of 5884 patients were included in the analysis, varying between countries from 21 to 1444. Survival was 320 (8%) in the CConly group and 174 (13%) in the FullCPR group. After adjustment for age, sex, location, rhythm, cause, time to scene, witnessed collapse and country, patients who received FullCPR had a significantly higher survival rate when compared to those who received CConly (adjusted odds ration 1.46, 95% confidence interval 1.17–1.83). Conclusion: In this analysis, FullCPR was associated with higher survival compared to CConly. Guidelines should continue to emphasise the importance of compressions and ventilations during resuscitation for patients who suffer OHCA and CPR courses should continue to teach both