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The studies considered graphene-based biomaterials dedicated for cardiovascular therapy. Reduced graphene oxide flakes were introduced into the porous structure of the polyelectrolyte based coatings. TEM analysis showed the presence of graphene flakes arranged parallel to the substrate surface, firmly connected to the porous coating. Biomaterials were subjected to a comprehensive diagnosis of the biological and material properties. The material behavior was simulated using finite element method. The coatings were deposited using layer by layer method. Mechanical analysis was done using Berkovich indenter geometry. They confirmed theoretical FEA based calculations, it was observed the coating stiffness incensement under the influence of introduced particles of graphene. The endanger of the bacteriology film formation was verified based on the E-coli and Staphylo coccus bacteria. Blood-material interaction was examined in the dynamic flow conditions. Bacteriological analysis showed reduced presence of bacteria after contact with the surface with introduced graphene flakes. Dynamic analyzes on blood showed high activation of the coagulation, strong platelets consumption and a strong immune response. It is caused by sharp edge of the single plane of the graphene flake. [ABSTRACT FROM AUTHOR]

Summary Background Churg-Strauss syndrome ( CSS) shares similarities with asthma and hypereosinophilic syndrome ( HES). Eicosanoids - important inflammatory and signaling molecules - are present in exhaled breath condensate ( EBC) and broncho-alveolar lavage fluid ( BALF). Objectives To assess eicosanoid profile both in EBC and BALF of CSS subjects searching for a pattern characteristic of this syndrome. Methods EBCs from 23 CSS patients, 30 asthmatics, 12 HES patients and 54 healthy controls ( HC) were assessed quantitatively for 19 eicosanoids by a high-performance liquid chromatography - tandem mass spectrometry ( HPLC- MS/ MS). In addition, in 21 of 23 CSS subjects and in nine asthmatics, eicosanoids were determined in BALF. Results EBC from CSS patients showed markedly elevated levels of 12- HETE as compared with other studied groups. BALF was characterized by a significant elevation of 12- HETE and its metabolite 12-tetranor HETE in CSS as compared with asthma. Clinical activity of CSS correlated with 12- HETE and its metabolites levels in BALF, but not in EBC. Conclusion and Clinical Relevance CSS is clearly distinguished from bronchial asthma, and HES by a marked increase in 12- HETE concentration in both EBC and BALF. This points to a possible new pathogenic mechanism in CSS and may help in future in establishing the diagnosis of CSS. [ABSTRACT FROM AUTHOR]

Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/ mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinylleukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity. [ABSTRACT FROM AUTHOR]

Cite this as: M. Sanak, Clinical & Experimental Allergy, 2011 (41) 2-5. [ABSTRACT FROM AUTHOR]

Background: A special regulatory role for prostaglandin E2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E2 and cysteinyl leucotrienes in patients with asthma. Methods: The urinary concentrations were determined of two main prostaglandin [2 metabolites (13,14-dihydro-15keto-PGE2 using a commercial enzyme immunoassay and 9,15-dioxo-11αhydroxy-2,3,4,5-tetranor-prostane-1,20-dioic acid by gas chromatography/mass spectrometry) and leucotriene E4 using an immunoassay. Determinations were performed at baseline and following oral aspirin and celecoxib challenges in two well-defined asthma phenotypes: aspirin-sensitive and aspirin-tolerant patients. Results: Aspirin precipitated bronchial reactions in all aspirin-sensitive patients but in none of the aspirin-tolerant patients. Celecoxib 400 mg was well tolerated by all patients except for one with aspirin-induced asthma. At baseline, the mean levels of prostaglandin E2 metabolites did not differ between the groups. Following different aspirin provocation doses, the mean levels of the two main prostaglandin E2 metabolites were decreased in the aspirin-tolerant group but remained unchanged in the aspirin-sensitive group. The dose of aspirin had no effect on the magnitude of the response on the prostaglandin [2 metabolites and its duration. In both groups, urinary prostaglandin E2 metabolites decreased following celecoxib challenge. No correlation was found between prostaglandin E2 metabolites and leucotriene E4. Conclusions: Aspirin-precipitated asthmatic attacks are not associated with changes in the systemic production of prostaglandin [2. In contrast, the systemic production of prostaglandin [2 becomes depressed by aspirin in non-sensitive patients. This different response might indicate COX-1-dependent prostaglandin E2 control of inflammatory cells in aspirin-induced asthma. Thus, PGE2 is released during the clinical reactions to aspirin through an alternative COX-2 pathway. The clinical implications of this finding are in line with current observations of good tolerance of the selective COX-2 inhibitors in aspirin-sensitive patients. [ABSTRACT FROM AUTHOR]

Background: The high-affinity receptor for immunoglobulin-E (IgE) (Fc ℇRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its α subunit (Fc ℇRI α) genetic variability in allergic diseases. Aims of the study: Mutational screening in the region of the Fc ℇRIα gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample. Methods: Allergic subjects were individuals with asthma or urticaria. Age- and sex-matched controls were randomly selected from a large population sample. Mutational screening was performed using a single-stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins. Results: Two linked polymorphisms −344 C>T and −95 T>C were found within the Fc ℇRI α gene. The allele −344 T frequency was 0.45 vs 0.37 ( P = 0.33), and the allele −95 C frequency was 0.26 in subjects vs 0.30 in controls ( P = 0.62). Serum IgE was significantly higher in subjects homozygous for the −344T allele (TT genotype) than in those carrying the −344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls. Conclusions: Our findings of genotype-related differences in IgE levels in allergic patients suggest an impact of −344 C>T but not −95 T>C gene polymorphism of Fc ℇRI α on total levels of IgE. The genetic variability in Fc ℇRI α at the −344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin. [ABSTRACT FROM AUTHOR]

In antiphospholipid syndrome (APS) the presence of anti-β2-glycoprotein I (β2GPI) antibodies is strongly associated with thromboembolic complications. It has been suggested that the common β2GPI Valine/Leucine247 (Val/Leu247)polymorphism could be found more commonly in APS and might influence the generation of anti-β2GPI antibodies. Therefore we studied β2 GPI Val/Leu247 single-nucleotide polymorphism (SNP) by PCR in 338 patients with various autoimmune diseases (46 with secondary and 84 with primary APS) and 147 sex and age-matched healthy controls. In all patients lupus anticoagulant, anticardiolipin and anti-β2GPI antibodies (both IgG and IgM) were also determined. All patients and controls were Caucasians. Frequencies of the SNP genotypes in patients did not depart from genetic equilibrum and did not differ from those found in controls. There was also no association between the presence of β2GPI Val/Leu247 genotypes and the presence or absence of lupus anticoagulant, anticardiolipin antibodies, anti-β2GPI antibodies or clinical APS symptoms in all patients studied. In conclusion, among the exclusively Caucasian, Polish population of autoimmune patients β2GPI Val/Leu247SNP has the same distribution as in healthy subjects and does not influence the production of anti-β2GPI antibodies. [ABSTRACT FROM AUTHOR]

Biochemical analysis of expiratory breath condensate is an emerging non-invasive technique for assessment of airway inflammation.We wondered whether application of expiratory breath condensate could facilitate diagnosis of aspirin-intolerant asthma and reproduce eicosanoids mediators' abnormalities described in this disease.We measured prostaglandins (PGs) E2, F2α, 9α11βF2 and iso-F2 by gas-chromatography/mass-spectrometry and cysteinyl leukotrienes (cys-LTs) by radioimmunoassay in breath condensates of asthmatic patients undergoing oral aspirin challenge. Fourteen patients with aspirin-induced asthma and 20 aspirin-tolerating asthmatics, most of them on chronic inhaled corticotherapy, were studied and compared with 10 healthy subjects. Additionally, plasma 9α11βPGF2, the metabolite of PGD2 and urinary leukotriene (LT) E4 were measured before and following the challenge.At baseline, PG did not differ between the groups, except for lower 9α11βPGF2 in aspirin-intolerant asthma. Their concentrations were not changed by the challenge. Breath condensate cys-LTs were similar in the groups studied at base, and after aspirin challenge increased only in aspirin-intolerant patients. Elevated baseline urinary LTE4 and its further increase following aspirin challenge was highly diagnostic for aspirin-intolerant asthma. The discriminatory value of cys-LTs increase in breath condensates was lower (72.8%) than either basal (99%) or post-challenge increase (94%) of urinary LTE4.In asthmatic patients on chronic corticotherapy measurement of urinary LTE4 excretion rather than cys-LTs in breath condensate is of greater value for diagnosis of aspirin hypersensitivity. [ABSTRACT FROM AUTHOR]

Background Eosinophilopoetic cytokine IL-5 enhances cysteinyl-leukotriene (cys-LT) synthesis in eosinophils in vitro. In patients with aspirin-induced asthma (AIA) bronchial biopsies revealed eosinophil infiltration and a marked increase in IL-5 positive cells. Objective We wondered whether in AIA patients the bronchial IL-5 increase is reflected in peripheral blood, and if so, whether it is related to overproduction of cys-LT. Methods In 11 stable patients with AIA, 32 with ATA (aspirin-tolerant asthma) and in 16 controls we measured serum IL-5 concentrations and urinary LTE4, believed to reflect global cys-LT production. Results Serum IL-5 was detectable in 12 of 43 asthmatics, but in none of the control subjects. It was highest in the ATA group and differed significantly from the controls. There was no significant difference in IL-5 levels between: (i) the asthmatic groups studied, and (ii) AIA patients and controls. No relationship was found between serum IL-5 and urinary cys-LT. Conclusion Overexpression of IL-5 reported in the airways of aspirin-sensitive patients with asthma was not reflected in their blood. If IL-5 affects cys-LT production, it is rather in the bronchi of the patients than in the blood. [ABSTRACT FROM AUTHOR]

The article offers information on urinary leukotriene E4 (uLTE4) excretion in asthma for which a comparison of HPLC mass spectrometry and enzymatic immunoassay (ELISA) is mentioned. It states that the purification of urine, by affinity extraction with monoclonal antibody can improve specificity. It discusses asthmatic tests of patients on which it reports that through the use of ELISA method, no difference between healthy subjects and asthmatics, who tolerated aspirin well, is noted.

Two FCER1A gene proximal promoter polymorphisms, –344C > T and –95T > C, both associated with total serum IgE and/or allergic disorders in Caucasians and East Asians, were shown to influence the gene expression in additive manner. In face of the rarity of other proximal promoter variants in Caucasians or their lack in East Asians, future investigations of the FCER1A locus in these ethnic groups should probably focus on three common haplotypes of the common –344C > T and –95T > C polymorphisms. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor ß chain gene, to airway hyper-responsiveness," by Y. K. Kim, H. W. Park, and J. S. Yang in the previous issue.

The article discusses a study that reveals that FCER1A and FCER1B polymorphism demonstrated an additive association with total serum immunoglobulin E (IgE) in allergic patients. FCER1A and FCER1B are the genes encoding subunits of the high-affinity IgE receptor. FCER1B -109TT controls tended to have higher serum IgE levels than subjects carrying the variant -109C allele.

Background Arachidonic acid metabolites regulate several aspects of airway function including inflammation, muscle contraction and mucous secretion. Objective The aim of this study was to evaluate concentration of selected 5-lipoxygenase- and cyclooxygenase-derived eicosanoids in exhaled breath condensate (EBC) during allergen-induced bronchoconstriction. Methods The study was performed on 24 allergic rhinitis/asthma patients sensitized to a house dust mite (HDM) Dermatophagoides pteronyssinus (Dp) and 13 healthy controls (HCs). Bronchial challenge with Dp extract was performed only in the allergic patients. EBC samples were collected before ( T0) and during Dp-induced bronchoconstriction ( TEAR). Eicosanoid concentration was measured using HPLC-tandem mass spectrometry. Results Significant bronchoconstriction after Dp challenge was demonstrated in 15 patients (Rs), while in 9 patients (NRs) no asthmatic response could be detected. At T0 the most abundant eicosanoids in EBC of HDM-allergic patients were LTB4 and 5-oxo-ETE, while in HCs EBC concentration of LTB4 was significantly greater than that of 5-oxo-ETE. Allergen challenge resulted in significant increase in EBC concentration of 5-oxo-ETE, LTD4 and 8-iso-PGE2 only in Rs. At TEAR, the relative change of 5-oxo-ETE concentration in EBC correlated with decrease of peripheral blood eosinophilia ( R = −0.774; P = .0012). Moreover, the relative increase of 5-oxo-ETE in EBC at TEAR significantly correlated with the severity of the subsequent late asthmatic response ( R = 0.683, P = .007). Conclusion Our study demonstrates significant up-regulation of 5-oxo-ETE synthesis in HDM-allergic patients and indicates possible involvement of that mediator in the pathogenesis of allergic asthma. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on the role of cyclooxygenase-1 and cyclooxygenase-2 in asthma pathogenesis. Use of selective inhibitors; Possibilities for anti-inflammatory treatment in patients with urticaria; Differences between aspirin and other non-steroid anti-inflammatory drugs.

Low-affinity IgE receptor gene ( FCER2) rs3760687 polymorphism was found to be associated with differential binding affinity of transcription factors Sp1 and Sp3 leading to altered transcriptional activity. Haplotypic interaction of functional FCER2 polymorphisms (rs28364072, rs2228137 and rs3760687) might potentially provide a background for genotype–phenotype associations previously observed for some rather non-functional FCER2 variants. [ABSTRACT FROM AUTHOR]

Background We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the −444C allele of the leukotriene C4 synthase gene ( LTC4S) was higher than in patients who tolerated aspirin well. Objectives To study the pattern of aspirin-induced urticaria (AIU) in two families, with special interest on the polymorphisms of LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes ( GSTM1 and GSTP1). Methods Of 74 patients with CIU and a history of aspirin hypersensitivity studied by us, two patients (probands) gave a family history of aspirin intolerance. Oral challenge tests with aspirin were carried out in members of these families. Genomic DNA samples were obtained from peripheral blood to study the polymorphisms of LTC4S, GSTM1 and GSTP1. Results In family 1 the aspirin challenge test confirmed AIU in three of five (60%) individuals, but in family 2 only in two of seven (29%). In both families, the variant genotypes of LTC4S (AC or CC) were present in the parents, but only one of them had CIU. In family 1, with both parents healthy, the three children had AIU; in two it was associated with variant LTC4S genotype. In family 2, urticaria following aspirin ingestion was present only with variant LTC4S genotype. In patients of both families with positive aspirin challenge test, deletion of the GSTM1 gene was present. Conclusions AIU aggregates in families inheriting the LTC4S−444C allele. Segregation of aspirin sensitivity in these families does not follow a clear Mendelian pattern. A common deletion of GSTM1, one of several enzymes involved in conjugation of a wide range of electrophilic substances with glutathione, was present in all individuals ascertained to have AIU. [ABSTRACT FROM AUTHOR]

Abstract Background Treatment with antileukotriene drugs results in clinical improvement in many, though not all, patients with asthma. It can be hypothesized that the subpopulation of asthmatic patients, characterized by aspirin intolerance and cysteinyl-leukotriene overproduction, might profit most from antileukotriene treatment. Materials and methods We compared the clinical response to montelukast in two well-matched groups of patients with mild asthma: 26 aspirin-intolerant asthmatics (AIAs) and 33 aspirin-tolerant asthmatics (ATAs). We also searched for possible predictors of the clinical response among the parameters reflecting the expression and production of cysteinyl-leukotrienes (cys-LTs). This was an 8-week, single-blind, placebo-controlled trial. Results Following a 3-week montelukast 10 mg day-1 treatment compared with placebo, there was a statistically significant reduction in the mean daytime and nocturnal asthma symptoms and β2 -agonist use, as well as a significant improvement in the morning and evening peak expiratory flows and quality of life. Both groups showed a similar significant improvement in the parameters studied. Clinical response did not correlate with the baseline urinary LTE4 excretion level. Improvement of asthma was observed mostly in patients with a low baseline and non-IL-5 inducible expression of LTC4 synthase (LTC4 S) mRNA in eosinophils. There was a trend toward a better response in carriers of LTC4 S allele C, but no relationship to the CC10 genetic polymorphism. Conclusions No difference in the clinical response to the montelukast treatment was observed between the AIAs and the ATAs. [ABSTRACT FROM AUTHOR]

Evaluates whether measurement in vitro of cysteinyl leukotrienes (Cys-LTs) release by isolated peripheral blood leucocytes, stimulated with acetyl salicylic acid, can be of use for aspirin-induced asthma (AIA) diagnosis. Administration of a cellular allergen stimulation test; Enzyme-linked immunosorbent assay of Cys-LTs; Differences between cys-LTs release by leucocytes from AIA and aspirin-tolerant asthma.

Summary: In vasculitis disorders, inflammation affects blood vessels. Granulomatosis with polyangiitis (GPA) is a chronic systemic vasculitis distinguished by the presence of anti‐proteinase‐3 autoantibodies (anti‐PR3). In this study we analyzed the molecular signature of human umbilical endothelial cells (HUVECs) in response to neutrophil‐derived extracellular vesicles (EVs). EVs were obtained from anti‐PR3‐activated neutrophils, purified and characterized by flow cytometry, nanoparticle tracking and miRNA screening. HUVECs were stimulated with EVs and miRNA/mRNA expression was measured. Cell culture media proteins were identified by antibody microarrays and selected cytokines were measured. Comparison of differentially expressed miRNAs/mRNAs between non‐stimulated and EV‐stimulated HUVECs revealed two regulatory patterns. Significant up‐regulation of 14 mRNA transcripts (including CXCL8, DKK1, IL1RL1, ANGPT‐2, THBS1 and VCAM‐1) was accompanied by 11 miRNAs silencing (including miR‐661, miR‐664a‐3p, miR‐377‐3p, miR‐30d‐5p). Significant down‐regulation was observed for nine mRNA transcripts (including FASLG, CASP8, STAT3, GATA3, IRAK1 and IL6) and accompanied by up‐regulation of 10 miRNAs (including miR‐223‐3p, miR‐142‐3p, miR‐211‐5p). Stimulated HUVECs released IL‐8, Dickkopf‐related protein 1 (DKK‐1), soluble interleukin (IL)‐1 like receptor‐1 (ST2), growth differentiation factor 15 (GDF‐15), angiopoietin‐2, endoglin, thrombospondin‐1 and vascular adhesion molecule‐1 (VCAM‐1). Moreover, transfection of HUVECs with mimics of highly expressed in EVs miR‐223‐3p or miR‐142‐3p, stimulated production of IL‐8, ST2 and endoglin. Cytokines released by HUVECs were also elevated in blood of patients with GPA. The most increased were IL‐8, DKK‐1, ST2, angiopoietin‐2 and IL‐33. In‐vitro stimulation of HUVECs by neutrophil‐derived EVs recapitulates contribution of endothelium in autoimmune vasculitis. Proinflammatory phenotype of released cytokines corresponds with the regulatory network of miRNAs/mRNAs comprising both EVs miRNA and endothelial cell transcripts. [ABSTRACT FROM AUTHOR]

Objectives: Neutrophil apoptosis is mandatory for resolving inflammation and is regulated by expression of pro- and anti-apoptotic genes. We studied neutrophils isolated from patients with granulomatosis with polyangiitis (GPA) to investigate apoptosis alterations and to identify transcriptional and circulating factors affecting this process.Method: We enrolled 36 patients (18 in active stage, 18 in remission) and 18 healthy controls. Circulating levels of tumour necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage migration inhibitory factor, plasminogen activator inhibitor-1, interferon-γ, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule-1, soluble Fas (sFas), sFas ligand, survivin, and pentraxin-3 (PTX3) were evaluated by enzyme-linked immunosorbent assay/Luminex; circulating apoptotic neutrophils by flow cytometry; and apoptosis-related gene transcripts by real-time polymerase chain reaction.Results: Patients had decreased fractions of circulating apoptotic neutrophils and delayed neutrophil apoptosis was present in vitro. Circulating levels of TNF-α, GM-CSF, sFas, and PTX3 were higher in GPA. Delayed neutrophil apoptosis was accompanied by decreased mRNA of pro-apoptotic genes and transcription factors (DIABLO, PMAIP1, BAX, CASP3, CASP7, RUNX3, E2F1, TP53) and increased anti-apoptotic CFLAR and BCL2A1 mRNA. TNF-α and sFas levels correlated with circulating apoptotic neutrophils and expression of apoptosis genes. Stimulation with TNF-α of neutrophils from controls significantly down-regulated E2F1 and CASP3 expression.Conclusions: Circulating neutrophils in GPA have anti-apoptotic phenotype involving both intrinsic and extrinsic pathways of apoptosis. This is accompanied by increased levels of circulating pro-survival factors (GM-CSF, TNF-α, sFas), independent of disease activity. Anti-apoptotic phenotype of neutrophils in GPA is reproduced by exposure to low concentrations of TNF-α. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to investigate the mechanisms of T helper type 17 (Th17) expansion in lupus nephritis (LN) patients, and to determine whether or not it is associated with impaired function of regulatory T cells (Treg). Major effector subsets of peripheral blood CD4+ T cells were assessed by flow cytometry in 33 LN patients with different activity of the disease and 19 healthy controls. The percentage of circulating Th17 cells was increased in LN (median = 1·2% of CD4+ compared to 0·6% in the control group, P < 0·01), while Treg cells remained unchanged (12·3 versus 12·1% in controls), resulting in a significantly lower Treg/Th17 ratio. Th17 expansion in the patient group was not related to LN activity, renal histology or blood and urine inflammatory biomarkers, but has been associated with a higher cumulative dose of cyclophosphamide. Treg cells in LN displayed mainly effector memory phenotype and expressed higher levels of transforming growth factor (TGF)‐β; however, their suppressant activity in lymphocyte proliferation assay was diminished compared to controls (~fourfold, P < 0·05). Co‐culture of Treg and conventional CD4+ T cells resulted in marked suppression of the Th1 subset in both of the groups studied, but also in a potent expansion of Th17 cells, which in LN was twofold higher, as in controls (P < 0·05). In conclusion, our results demonstrate that Th17 expansion in LN is not increased during disease exacerbation, but is related to chronic immunosuppressive therapy. This immune signature is probably linked to the abnormal function of Treg cells, which were less suppressive in LN patients and even facilitated differentiation of Th17 cells. Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus associated with an imbalance between T‐regulatory (Treg) and Th17 responses. Here, we show that Th17 expansion develops in a subgroup of LN patients, but is not related to disease activity, renal histology, or blood and urine inflammatory biomarkers. This immune signature is likely linked to the abnormal function of Treg cells, which were less suppressive in LN patients and even facilitated expansion of Th17 cells. [ABSTRACT FROM AUTHOR]

Introduction Renal involvement is one of the most serious manifestations of systemic lupus erythematosus, but non-invasive assessment of inflammatory response in kidneys is challenging. In this study we aimed to validate markers of active lupus nephritis (LN) using urine immune profiling. Methods Urine and serum cytokines (17-plex array) and urine mRNA expression (∼40 immune and glomerular injury genes) were measured in LN patients with active disease (n = 17) during remission (n = 16) and in healthy subjects (n = 18). Results Urine and serum levels of CCL2, CCL5 and CXCL10 were elevated in active LN as compared with disease remission (best discrimination for urine CXCL10 and CCL2) and correlated with LN activity. In the active disease, urinary cell transcriptome showed marked upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), and type-1 immunity-related genes (e.g. CD3G, CD4, TBX21, IFNG). An active pattern of gene expression was also observed in four patients in remission, who had moderately increased urinary leucocyte count. Two patients from this group developed renal exacerbation during the following 3 months. Markers of type-17 immune axis (e.g. IL-17A) were not significantly increased in active LN. Conclusions Active LN patients were characterized by marked increase of proinflammatory mediators in the urine. Urine cytokines (CCL2 and CXCL10) and type-1 T-cell-related gene markers in the urine sediment had similar diagnostic performance in detection of active LN. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is an important risk factor of asthma development and is responsible for severe respiratory tract infections. However, the influence of RSV infection on barrier function of bronchial epithelial cells in vitro and in vivo is still unclear. The aim of this study was to analyse the role of RSV in tight junction (TJ) regulation and to compare epithelial integrity between asthmatic and healthy individuals upon RSV infection. Healthy and asthmatic human bronchial epithelial cells (HBECs) were differentiated at air-liquid interface (ALI) and infected with RSV and ultraviolet (UV)-irradiated RSV. TJ expression and their integrity were analysed by quantitative polymerase chain reaction (qPCR), transepithelial resistance (TER) and paracellular flux. To determine the effect in vivo, BALB/c mice were infected intranasally with RSV or UV-irradiated RSV A2. Bronchoalveolar lavage and TJ integrity were analysed on days 1, 2, 4 and 6 post-infection by qPCR, bioplex and confocal microscopy. RSV increased barrier integrity in ALI cultures of HBEC from healthy subjects, but no effect was found in HBECs from asthmatics. This was not associated with an increase in TJ mRNA expression. In vivo, RSV induced lung inflammation in mice and down-regulated claudin-1 and occludin mRNA expression in whole lungs. Surprisingly, RSV infection was not observed in bronchial epithelial cells, but was found in the lung parenchyma. Decreased expression of occludin upon RSV infection was visible in mouse bronchial epithelial cells in confocal microscopy. However, there was no regulation of claudin-1 and claudin-7 at protein level. [ABSTRACT FROM AUTHOR]

The article presents a comparative study of FCER1A gene exon 1A polymorphisms in Japanese and Polish subjects. FCER1A stands for polymorphisms of the gene encoding α-subunit of the high affinity immunoglobulin E receptor. It was suggested that FCER1A was involved in the pathogenesis of allergic disorders.

Patients with familial hypercholesterolemia (FH) are at increased risk of premature cardiovascular disease. We compared factors associated with the presence of carotid plaques and carotid intima–media thickness (cIMT), markers of subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41 ± 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age, apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1 unit change 1.03, P = .005), high-density lipoprotein cholesterol (HDL-C; OR per 1 standard deviation [SD] change 0.59, P = .015), and non-HDL-C (OR per 1SD change 1.53, P = .04) were significantly associated with the presence of plaques. The cIMT correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C-reactive protein, creatinine, γ-glutamyl transpeptidase, and alanine transaminase (P < .001). Regression analysis revealed that cIMT was significantly associated with apoB, SBP, and WHR. These results confirm the role of apoB-containing lipoproteins and low HDL-C with the presence of carotid plaques and apoB, BP, and WHR with cIMT. [ABSTRACT FROM AUTHOR]

Background Induced sputum ( IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. The specific role of induced sputum supernatant ( ISS) endogenous bioactive lipid mediators in subtypes of asthma is not well understood. Objective To investigate the interactions between airway inflammation and clinical phenotypes of asthma, we integrated induced sputum supernatant ( ISS) eicosanoids and quantitative assessment of infiltrating cells into new subtypes with the means of latent class analysis ( LCA). Methods One hundred and thirty-nine asthmatics with and without aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids. Nineteen variables covering clinical characteristics, IS inflammatory cells and eicosanoids were considered in the LCA. Results Four phenotypic asthma classes were distinguished. Class 1 with mild-to-moderate asthma, chronic rhinosinusitis ( CRS), high PGA2 in ISS and almost equal distribution of inflammation cell patterns. Class 3 subjects also had mild-to-moderate asthma but without upper airway symptoms. Induced sputum was often paucigranulocytic with low levels of lipid mediators. Classes 2 and 4 represented severe asthma with CRS and impaired lung function despite high doses of steroids. High blood and sputum eosinophilia was in line with high cysteinyl leukotrienes and PGD2 in ISS only in class 2. Class 4 subjects tended to have increased sputum neutrophilia and PGE2 in ISS. Aspirin hypersensitivity was most frequent among class 2 subjects. Conclusions & Clinical Relevance The LCA revealed four distinct asthma classes differing in eicosanoid pathways. [ABSTRACT FROM AUTHOR]

Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment. [ABSTRACT FROM AUTHOR]

The work was related to the development of novel methods in designing and fabrication of thin, porous, tissue-like coatings. The surface modification was designed to create an environment for the appropriate cell growth. The originally designed system was established to prepare porous, synthetic coatings. The dedicated software was elaborated to control the sequential coating deposition based on the electrostatic interaction. The finite elements method (FEM) was used to determine structural and mechanical properties of the coatings. The numerical model was verified experimentally. The performed simulation predicted the coating stabilization by the graphene nanoparticles. Graphene was introduced as a stabilizer of the polymer coating. The elaborated automatic system allowed preparation the porous coatings, repetitively. Coatings were stabilized by the cross-linking chemical reaction using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide. Nanoparticles were introduced by means of the electrostatic interaction. Mechanical analysis revealed an influence of the porous structure modification on the coating stiffness. Dynamic tests on blood subjected to the aortic flow showed antithrombogenic properties of the elaborated coatings. [ABSTRACT FROM AUTHOR]

Background Pro- and anti-inflammatory metabolites of arachidonic acid - eicosanoids - participate in skin homeostasis, affecting the growth and differentiation of keratinocytes. Alterations of 12-lipoxygenase ( LOX) and 15- LOX and their metabolites have been described in the epidermis of patients with psoriasis, but systemic production of 12- LOX and 15- LOX eicosanoids has not been studied in the disease. Objectives To ascertain the frequencies of the genetic variants ALOX12 rs1126667 and ALOX15 rs11568070 in cases and controls, and to compare urinary metabolites of 12( S)-hydroxyeicosatetraenoic acid ( HETE) between patients with psoriasis and healthy controls. Methods Patients with psoriasis ( n = 200) were stratified depending on the severity of their dermal lesions. Genotyping was performed using a 5′-nuclease real-time assay. The concentrations of 12( S)- HETE, its metabolites and 15( S)- HETE were determined in urine samples using high-performance liquid chromatography-tandem mass spectrometry. Results Tetranor-12( S)- HETE metabolite excretion was significantly higher in urine of patients with psoriasis, while excretion of 12( S)- HETE was decreased. Neither 12( S)- HETE nor tetranor-12( S)- HETE correlated with the type of disease or severity score. No difference in urinary 15( S)- HETE was found between the study groups. Genotype distribution of the ALOX12 rs1126667 or ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity. Conclusions Systemic metabolism of 12( S)- HETE is accelerated in psoriasis because excretion of the tetranor-12( S)- HETE inactivation product is elevated. No correlation with the severity or extent of psoriasis is detectable. We propose that in patients with psoriasis, 12( S)- HETE to tetranor-12( S)- HETE conversion could be at least a marker for this disease, in which inflammation of the skin can induce microsomal beta-oxidation of this eicosanoid. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs ( NSAIDs) are the medications most frequently involved in hypersensitivity drug reactions. Because NSAIDs are prescribed for many conditions, this is a world-wide problem affecting patients of all ages. Various hypersensitivity reactions have been reported, mainly affecting the skin and/or the respiratory airways. The most frequent of these is acute urticaria, which can be induced by several different NSAIDs. Both specific and non-specific immunological pathways have been proposed as underlying mechanisms. This review presents the clinical phenotypes and the drugs involved in NSAID hypersensitivity. Five major clinical syndromes can be distinguished: aspirin-exacerbated respiratory disease ( AERD), aspirin-exacerbated cutaneous disease ( AECD), multiple NSAID-induced urticaria/angioedema (MNSAID-UA), single NSAID-IgE reactions and single NSAID T cell responses. However, further classification is possible within these five major entities, by detailed descriptions of the clinical characteristics enabling more phenotypes to be defined. This detailed differentiation now seems required in order to undertake appropriate pharmacogenetic studies. [ABSTRACT FROM AUTHOR]

Background Multiple NSAID-induced urticaria/angioedema ( MNSAID- UA) is an entity well differentiated from aspirin-exacerbated respiratory disease ( AERD), although no detailed phenotype analysis has yet been performed. The objective was to evaluate the functional characteristics of MNSAID- UA subjects by analyzing the response to nasal lysine-aspirin challenge and measurement of nasal inflammatory mediator release compared with AERD subjects and controls. Methods The study included 85 subjects with confirmed hypersensitivity to NSAIDs (≥3 episodes with >2 different NSAIDs or positive drug provocation) with either cutaneous ( MNSAID- UA, n = 25) or respiratory manifestations ( AERD, n = 60) and 30 tolerant controls (15 aspirin-tolerant asthmatic patients and 15 healthy controls). Nasal lavages at 0, 15, 60, and 120 min after lysine-aspirin challenge were analyzed for ECP, tryptase, PGE2, PGD2, LTD4, and LTE4. Results Lysine nasal challenge was positive in 80% of the AERD cases but positive only in 12% of the MNSAID- UA group. MNSAID- UA subjects showed no changes in nasal ECP, whereas subjects with AERD had increased levels of ECP, with the highest peak at 15 min after challenge ( P < 0.05). Tryptase levels were higher in AERD compared with MNSAID- UA and controls with the highest release of tryptase at 60 min ( P < 0.05). Significant increases in PGD2, LTD4, and LTE4 were observed in AERD (at 60 min for PGD2, LTD4, and LTE4) but not in MNSAID- UA or control subjects ( P < 0.05). Conclusions Data support the observation that MNSAID- UA, although sharing a common response with AERD to COX inhibitors, seems to have a distinctive phenotype, based on the response to nasal challenge and the release of inflammatory mediators. [ABSTRACT FROM AUTHOR]

An abstract of the article "Aspirin tolerance and leukotriene biosynthesis in Churg-Strauss syndrome," by W. Szczeklik, L. Mastalerz, B. Sokolowska, M. Sanak and E. Nizankowska-Mogilnicka is presented.