First Author: Yael Graif
All Authors: Graif Y, Romano-Zelekha O, Livne I, Green MS, Shohat T
Journal Title: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Abstract: The question of whether atopic diseases are a risk factor for allergic reactions to insect sting is still unresolved. The aim of this study was to evaluate the association between atopic diseases (asthma, allergic rhinitis, atopic eczema) and allergic reactions to insect stings among schoolchildren in Israel. A self-report questionnaire of the International Study of Asthma and Allergies in Childhood was administered to a national sample of 13-14-yr-old schoolchildren. Questions regarding reactions to insect stings were added. A total of 10,021 questionnaires were available for analysis. Among the children who reported insect stings (56.3%), the prevalence of current asthma was 6.0%, of allergic rhinitis, 10.5%, and of atopic eczema, 8.7%, with no significant differences from the whole study population. Among children with any of the atopic diseases, 36.9% reported an allergic reaction to insect sting compared to 24.8% of the non-atopic children (p < 0.0001). On multivariate analysis, asthma, allergic rhinitis, and atopic eczema were found to be significant risk factors for allergic reactions of any severity. Children in the atopic group had a significantly higher rate of severe allergic reactions than the non-atopic children, and relatively higher rates of milder ones (p < 0.0001). Asthmatic patients with severe allergic reactions had more parameters of severe asthma than asthmatic patients with mild or no reactions. In conclusions, allergic diseases are associated with a higher rate and greater severity of allergic reactions to insect sting in children. The severity of the allergic reaction is related to the severity of the asthma symptoms.
Authors: Koçluk Y, Alyamaç Sukgen E
Abstract: This study aims to report the differences in the findings of epidemic keratoconjunctivitis (EKC) between premature babies and their families at an outbreak of viral conjunctivitis.In this prospective observational study, premature babies (25 patients) who were diagnosed with EKC and the family members (30 patients, mother, father, or grandmother/father) who had EKC after contacting them were monitored closely. Patients were divided into two groups as preterm babies (group 1) and adults (group 2).The present study investigated particularly subepithelial corneal infiltrates (SEI) occurrence after EKC, which was searched for at each visit in the 2nd week, 1st month, and 3rd month after EKC. Distribution of SEI in two groups was statistically significant at each visit (<0.0001). There was more SEI in group 2.None of the preterm cases were found to have SEI after EKC.
Authors: Wiszniewska M, Walusiak-Skorupa J
Abstract: Work-exacerbated asthma (WEA) is asthma worsened by workplace exposures, although the asthma is not caused by sensitizers in the work environment.To evaluate the frequency of WEA in bakers reporting work-related respiratory symptoms and the usefulness of diagnostic tests in differentiating WEA from occupational asthma (OA).The study group included 393 bakers reporting respiratory symptoms at the workplace. In all patients, questionnaire, spirometry, skin prick tests (SPTs), and evaluation of serum total and specific IgE levels were performed. Recognition of OA was based on a specific inhalation challenge test.Occupational asthma was found in 44.5% of patients, whereas WEA was recognized in 16%. The latency period was 11.2 ± 8.2 years in patients with OA vs 13.3 ± 9.7 years in those with WEA. Sixty percent of patients with OA and 50.8% of those with WEA had positive SPT reactions to common allergens; occupational SPT results were positive in 74.9% and 34.9%, respectively. Specific IgE to flours were found in 61.7% of patients with OA and 28.6% of those with WEA. In addition, OA frequently coexisted with occupational rhinitis (53.7% of patients), whereas WEA and rhinitis were found in 31.7% of patients.Work-exacerbated asthma was diagnosed in 16% of bakers who reported allergic respiratory symptoms. The specific challenge test for occupational allergens should be performed in bakers with suspected work-related asthma, because an assessment of sensitization (SPT to occupational allergens, evaluation of specific IgE) is not specific enough to differentiate OA from WEA.
Authors: Hadeiba H, Locksley RM
Abstract: To study the effects of chronic Ag deposition in the airway mucosa on CD4(+) T cell priming and subsequent airway disease, transgenic mice were generated that expressed OVA under the control of the surfactant protein C promoter. CD4 T cells from these mice were tolerant to OVA but this was overcome among spleen CD4 T cells by crossing to OVA-specific DO11.10 TCR-transgenic mice. Lungs from the double-transgenic mice developed lymphocytic infiltrates and modest mucus cell hyperplasia. Infiltrating cells were unaffected by the absence of either Rag-1 or Stat6, although the latter deficiency led to the disappearance of mucus. In the lung of double-transgenic mice, a large number of Ag-specific CD4 T cells expressed CD25 and functioned as regulatory T cells. The CD25(+) CD4 T cells suppressed proliferation of CD25(-) CD4 T cells in vitro and inhibited type 2 immune responses induced by aerosolized Ags in vivo. Despite their ability to suppress allergic type 2 immunity in the airways, however, CD25(+) CD4 regulatory T cells had no effect on the development of bronchial hyperreactivity.
Authors: Gruber A, Brocker T
Abstract: The sizes of peripheral T cell pools are regulated by competition for environmental signals within a given ecological T cell niche. Cytokines and MHC molecules have been identified as resources for which naive T cells compete to proliferate homeostatically in lymphopenic hosts to fill up their respective compartments. However, it still remains unclear to what extent CD4 and CD8 T cells intercompete for these resources and which role dendritic cells (DC) play in this scenario. Using transgenic mice in which only DC express MHC class I, we demonstrate that this type of APC is sufficient to trigger complete homeostatic proliferation of CD8 T cells in vivo. However, normal numbers of endogenous naive CD4 T cells, but not CD25(+)CD4(+) T regulatory cells, efficiently suppress this expansion in vivo. These findings identify DC as a major resource and a possible target for homeostatic competition between naive CD4 and CD8 T cells.
Authors: Oei GT, Aslami H, Kerindongo RP, Steenstra RJ, Beurskens CJ, Tuip-de Boer AM, Juffermans NP, Hollmann MW, Preckel B, Weber NC
Abstract: Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150?mg/kg) and diazepam (1.5?mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60?min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1?) were found after 30 or 60?min of helium inhalation, in comparison to control. 30?min of helium increased mRNA levels of CINC-3, IL-1?, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-?) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.
Authors: Ehrlich P,
Authors: Nair AS, Shishodia S, Ahn KS, Kunnumakkara AB, Sethi G, Aggarwal BB
Abstract: Deguelin, a constituent of the bark of the African plant Mundulea sericea (Leguminosae), exhibits antiproliferative and anticarcinogenic activities through a mechanism that is not well understood. Because various steps in carcinogenesis are regulated by NF-kappaB, we postulated that the activity of deguelin is mediated through this transcription factor. We found that deguelin suppressed NF-kappaB activation induced by carcinogens, tumor promoters, growth factors, and inflammatory stimuli. This suppression was not cell-type specific, because NF-kappaB activation was suppressed in both lymphoid and epithelial cells. Moreover, constitutive NF-kappaB activation was also blocked by deguelin. The suppression of TNF-induced NF-kappaB activation by deguelin occurred through the inhibition of the activation of IkappaBalpha kinase, leading to sequential suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Deguelin also suppressed the NF-kappaB reporter activity induced by TNFR1, TNFR-associated death domain, TNFR-associated factor 2, and IkappaBalpha kinase, but not that induced by p65. The inhibition of NF-kappaB activation thereby led to the down-regulation of gene products involved in cell survival, proliferation, and invasion. Suppression of these gene products by deguelin enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular invasion. Our results demonstrate that deguelin inhibits the NF-kappaB activation pathway, which may explain its role in the suppression of carcinogenesis and cellular proliferation.
Authors: Agarwal V, Ahl J, Riesbeck K, Blom AM
Abstract: Streptococcus pneumoniae (pneumococcus) is a major human pathogen, which evolved numerous successful strategies to colonize the host. In this study, we report a novel mechanism of pneumococcal-host interaction, whereby pneumococci use a host complement protein C1q, primarily involved in the host-defense mechanism, for colonization and subsequent dissemination. Using cell-culture infection assays and confocal microscopy, we observed that pneumococcal surface-bound C1q significantly enhanced pneumococcal adherence to and invasion of host epithelial and endothelial cells. Flow cytometry demonstrated a direct, Ab-independent binding of purified C1q to various clinical isolates of pneumococci. This interaction was seemingly capsule serotype independent and mediated by the bacterial surface-exposed proteins, as pretreatment of pneumococci with pronase E but not sodium periodate significantly reduced C1q binding. Moreover, similar binding was observed using C1 complex as the source of C1q. Furthermore, our data show that C1q bound to the pneumococcal surface through the globular heads and with the host cell-surface receptor(s)/glycosaminoglycans via its N-terminal collagen-like stalk, as the presence of C1q N-terminal fragment and low m.w. heparin but not the C-terminal globular heads blocked C1q-mediated pneumococcal adherence to host cells. Taken together, we demonstrate for the first time, to our knowledge, a unique function of complement protein C1q, as a molecular bridge between pneumococci and the host, which promotes bacterial cellular adherence and invasion. Nevertheless, in some conditions, this mechanism could be also beneficial for the host as it may result in uptake and clearance of the bacteria.
Authors: Zhou H, Chen M, Zhang G, Ye RD
Abstract: Serum amyloid A (SAA) is known as an acute-phase protein and a biomarker for inflammatory diseases. Published studies have shown that SAA possesses proinflammatory cytokine-like activity and is chemotactic for phagocytes, but the structural basis for these activities remains unidentified. In this article, we report that truncated SAA1 proteins lacking N- and C-terminal sequences exhibit reduced proinflammatory activity and strongly suppress LPS-induced expression of IL-1?, IL-6, and TNF-? in macrophages. A truncated SAA1 containing aa 11-58 was examined further and found to facilitate p38 MAPK phosphorylation while reducing LPS-stimulated phosphorylation of ERK and JNK. In LPS-challenged mice, aa 11-58 reduced the severity of acute lung injury, with significantly less neutrophil infiltration in the lungs and attenuated pulmonary expression of IL-1?, IL-6, and TNF-?. Coadministration of aa 11-58 markedly improved mouse survival in response to a lethal dose of LPS. A potent induction of IL-10 was observed in a TLR2-dependent, but TLR4-independent, manner in macrophages stimulated with aa 11-58. However, the aa 11-58 fragment of SAA1 was unable to induce chemotaxis or calcium flux through formyl peptide receptor 2. These results indicate that the N- and C-terminal sequences contain structural determinants for the proinflammatory and chemotactic activities of SAA1, and their removal switches SAA1 to an anti-inflammatory role. Given that proteolytic processing of SAA is associated with the pathological changes in several diseases, including secondary amyloidosis, our findings may shed light on the structure-function relationship of SAA1 with respect to its role in inflammation.
Authors: Salma N, Julie L, Boutahar B, Sylvie LN, Eleonore B, Fabien LN, Elisabeth P, Sandrine JJ, Francis C, Sophie H, Yves R
Abstract: Patients with antiphospholipid antibodies (APLA) are predisposed to develop thrombosis, however the standardization of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein I (?2-GPI) Ab assays are challenging. Therefore we decided to test the performance of a new chemiluminescent assay (CLIA), and assayed aCL and a?2-GPI IgG/M in serum from 120 healthy individuals, 108 patients with idiopathic venous thrombosis, 78 patients with antiphospholipid syndrome (APS), and 64 non-thrombotic APLA-carriers using CLIA IDS-iSYS. Very good (aCL/a?2-GPI IgG) to moderate (aCL/a?2-GPI IgM) agreement with a commercial and an in house ELISA assay were observed and, in particular, CLIA demonstrated the highest sensitivity in a?2-GPI IgG detection. Finally, aCL/a?2-GPI Ab capacity to predict the thrombotic risk was tested showing for CLIA a significant odds ratio (OR) when considering double positivity for aCL/a?2-GPI IgG, aCL IgG at high levels, and a?2-GPI IgG at high levels. In conclusion, CLIA improves a?2-GPI IgG detection and thrombotic risk assessment.