Browsing by Subject "IGE"

Sort by: Order: Results:

Now showing items 1-14 of 14
  • Palosuo, Kati; Karisola, Piia; Savinko, Terhi; Fyhrquist, Nanna; Alenius, Harri; Mäkelä, Mika J. (2021)
    BACKGROUND: Egg allergy is the second most common food allergy in children. Persistent food allergy increases the risk of anaphylaxis and reduces the quality of life. OBJECTIVE: To determine the efficacy of oral immunotherapy (OIT) with raw egg white powder and study its effects on humoral responses in children with persistent egg allergy. METHODS: Fifty children aged 6 to 17 years with egg allergy, diagnosed by double-blind, placebo-controlled food challenge, were randomized 3:2 to 8 months of OIT with a maintenance dose of 1 g of egg white protein or 6 months of avoidance after which the avoidance group crossed over to OIT. We examined changes in IgE, IgG4, and IgA concentrations to Gal d 1-4 during OIT compared with avoidance and assessed clinical reactivity at 8 and 18 months. RESULTS: After 8 months, 22 of 50 children (44%) on OIT and 1 of 21 (4.8%) on egg avoidance were desensitized to the target dose, 23 of 50 (46%) were partially desensitized (dose
  • Palmu, Tiina; Lehtonen, Jussi; Korhonen, Laura; Virtanen, Suvi M.; Niemelä, Onni; Toppari, Jorma; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Laitinen, Olli H.; Lönnrot, Maria; Hyöty, Heikki (2021)
    Background Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association between EVs and allergic sensitization and disease in early childhood. Methods The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and identified with the ISAAC questionnaire. We screened for the presence of serotype-specific antibodies against 41 EVs at 1-5 years of age and assessed their association with allergic sensitization and disease. Results The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95% CI 0.36-0.99), p = .048. Conclusion This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.
  • Kukkonen, Anna Kaarina; Pelkonen, Anna Susanna; Edelman, Sanna Marika; Kauppi, Paula Maria; Mäkelä, Mika Juhani (2018)
    Background: Venom immunotherapy is effective in preventing systemic allergic reactions (SARs), but the diagnosis of venom allergy is problematic. Objective: To compare the performance of component-resolved diagnosis and conventional tests in patients referred for venom immunotherapy. Methods: We measured serum-specific immunoglobulin E to yellowjacket and honeybee venoms (Ves v 1 and Ves v 5 and Api m 1), cross-reactive carbohydrate determinants, serum basal tryptase (ImmunoCAP, ThermoFisher Scientific, Uppsala, Sweden), and skin prick test reactions in 84 patients referred to receive venom immunotherapy. History of SAR and its severity were evaluated. Results: Of the 78 patients with suspected yellowjacket venom (YJV) allergy, a history of SAR was confirmed in 47 (60%) and 31 (40%) had a non-SAR reaction. The most accurate tests to confirm venom allergy after a SAR were serum-specific immunoglobulin E to yellowjacket whole-venom extract spiked with Ves v 5 (area under the curve 0.87, 95% confidence interval 0.77-0.97, P <.001) and Ves v 5 (area under the curve 0.86, 95% confidence interval 0.76-0.96, P <.001). Sensitization to Ves v 1 was infrequent and its area under the curve was low (0.62, 95% confidence interval 0.47-0.76, P = .106). Sensitivity of the YJV skin prick test was 86%, but its specificity was low at 54%. Double sensitization to yellowjacket and honeybee occurred frequently in skin prick tests. Of the patients without a SAR, 26% showed a positive reaction to YJV in any serum test and 46% showed a positive reaction in skin tests. Conclusion: Specific immunoglobulin E to the YJV spiked with Ves v 5 confirmed the allergy after a SAR. A history of SAR should be confirmed before testing, because venom sensitization is frequent in other types of reactions. (C) 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • Vultaggio, Alessandra; Agache, Ioana; Akdis, Cezmi A.; Akdis, Mubeccel; Bavbek, Sevim; Bossios, Apostolos; Bousquet, Jean; Boyman, Onur; Chaker, Adam M.; Chan, Susan; Chatzipetrou, Alexia; Feleszko, Wojciech; Firinu, Davide; Jutel, Marek; Kauppi, Paula; Klimek, Ludger; Kolios, Antonios; Kothari, Akash; Kowalski, Marek L.; Matucci, Andrea; Palomares, Oscar; Pfaar, Oliver; Rogala, Barbara; Untersmayr, Eva; Eiwegger, Thomas (2020)
    The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
  • Xu, Cheng-Jian; Soderhall, Cilla; Bustamante, Mariona; Baiz, Nour; Gruzieva, Olena; Gehring, Ulrike; Mason, Dan; Chatzi, Leda; Basterrechea, Mikel; Llop, Sabrina; Torrent, Maties; Forastiere, Francesco; Fantini, Maria Pia; Carlsen, Karin C. Lodrup; Haahtela, Tari; Morin, Andreanne; Kerkhof, Marjan; Merid, Simon Kebede; van Rijkom, Bianca; Jankipersadsing, Soesma A.; Bonder, Marc Jan; Ballereau, Stephane; Vermeulen, Cornelis J.; Aguirre-Gamboa, Raul; de Jongste, Johan C.; Smit, Henriette A.; Kumar, Ashish; Pershagen, Goran; Guerra, Stefano; Garcia-Aymerich, Judith; Greco, Dario; Reinius, Lovisa; McEachan, Rosemary R. C.; Azad, Raf; Hovland, Vegard; Mowinckel, Petter; Alenius, Harri; Fyhrquist, Nanna; Lemonnier, Nathanael; Pellet, Johann; Auffray, Charles; van der Vlies, Pieter; van Diemen, Cleo C.; Li, Yang; Wijmenga, Cisca; Netea, Mihai G.; Moffatt, Miriam F.; Cookson, William O. C. M.; Anto, Josep M.; Kere, Juha (2018)
    Background DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p Interpretation Reduced whole-blood DNA methylation at 14 CpG sites acquired after birth was strongly associated with childhood asthma. These CpG sites and their associated transcriptional profiles indicate activation of eosinophils and cytotoxic T cells in childhood asthma. Our findings merit further investigations of the role of epigenetics in a clinical context.
  • Uotila, Riikka; Röntynen, Petteri; Pelkonen, Anna S.; Voutilainen, Helena; Kaarina Kukkonen, Anna; Mäkelä, Mika J. (2020)
  • Loo, Evelyn Xiu Ling; Lau, Hui Xing; Suaini, Noor Hidayatul Aini; Wong, Lydia Su Yin; Goh, Anne Eng Neo; Teoh, Oon Hoe; Van Bever, Hugo P. S.; Shek, Lynette Pei-chi; Lee, Bee Wah; Tan, Kok Hian; Godfrey, Keith M.; Eriksson, Johan Gunnar; Chong, Yap Seng; Tham, Elizabeth Huiwen (2021)
  • Haahtela, T.; Laatikainen, T.; Alenius, H.; Auvinen, P.; Fyhrquist, N.; Hanski, I.; von Hertzen, L.; Jousilahti, P.; Kosunen, T. U.; Markelova, O.; Mäkelä, M. J.; Pantelejev, V.; Uhanov, M.; Zilber, E.; Vartiainen, E. (2015)
    The Finnish and Russian Karelia are adjacent areas in northern Europe, socio-economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non-existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti-inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10-year National Allergy Programme was started in 2008 to combat the epidemic in Finland.
  • Karisola, Piia; Palosuo, Kati; Hinkkanen, Victoria; Wisgrill, Lukas; Savinko, Terhi; Fyhrquist, Nanna; Alenius, Harri; Mäkelä, Mika J. (2021)
    We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1-4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.
  • Hose, Alexander J.; Depner, Martin; Illi, Sabina; Lau, Susanne; Keil, Thomas; Wahn, Ulrich; Fuchs, Oliver; Pfefferle, Petra Ina; Schmausser-Hechfellner, Elisabeth; Genuneit, Jon; Lauener, Roger; Karvonen, Anne M.; Roduit, Caroline; Dalphin, Jean-Charles; Riedler, Josef; Pekkanen, Juha; von Mutius, Erika; Ege, Markus J.; Bauer, Carl Peter; Forster, Johannes; Zepp, Fred; Wahn, Volker; Schuster, Antje; Bergmann, Renate L.; Bergmann, Karl E.; Reich, Andreas; Grabenhenrich, Linus; Schaub, Bianca; Loss, Georg J.; Renz, Harald; Kabesch, Michael; Roponen, Marjut; Hyvarinen, Anne; Tiittanen, Pekka; Remes, Sami; Braun-Fahrlander, Charlotte; Frei, Remo; Kaulek, Vincent; Dalphin, Marie-Laure; Doekes, Gert; Blumer, Nicole; Frey, Urs; MAS Study Grp; PASTURE Study Grp (2017)
    Background: Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. Objective: We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Methods: Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. Results: The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-gamma ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. Conclusions: LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.
  • Kauppila, Tiina Kaisa; Paassilta, Marita; Kukkonen, Anna Kaarina; Kuitunen, Mikael; Pelkonen, Anna S.; Makela, Mika J. (2019)
    Background: The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study. Methods: During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1 year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed >= 2 dL of milk daily, while the failure group consumed Results: Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed >= 2 dL of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P <0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = 0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = 0.01). Conclusion: More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.
  • Lehtimaki, Jenni; Sinkko, Hanna; Hielm-Bjorkman, Anna; Laatikainen, Tiina; Ruokolainen, Lasse; Lohi, Hannes (2020)
    Both humans and pet dogs are more prone to develop allergies in urban than in rural environments, which has been associated with the differing microbial exposures between areas. However, potential similarities in the microbiota, that associate with environmental exposures, in allergic dogs and owners has not been investigated. We evaluated skin and gut microbiota, living environment, and lifestyle in 168 dog-owner pairs. Due to partly different manifestations of allergies between species, we focused on aeroallergen sensitized humans and dogs with owner-reported allergic symptoms. Our results agree with previous studies: dog-owner pairs suffered simultaneously from these allergic traits, higher risk associated with an urban environment, and the skin, but not gut, microbiota was partly shared by dog-owner pairs. We further discovered that urban environment homogenized both dog and human skin microbiota. Notably, certain bacterial taxa, which were associated with living environment and lifestyle, were also related with allergic traits, but these taxa differed between dogs and humans. Thus, we conclude that dogs and humans can be predisposed to allergy in response to same risk factors. However, as shared predisposing or protective bacterial taxa were not discovered, other factors than environmental microbial exposures can mediate the effect or furry dog and furless human skin select different taxa.
  • Rouvinen, Juha; Jänis, Janne; Laukkanen, Marja-Leena; Jylhä, Sirpa; Niemi, Merja; Päivinen, Tero; Mäkinen-Kiljunen, Soili; Haahtela, Tari Markku Kallevi; Soderlund, Hans; Takkinen, Kristiina (2010)
  • Geisslitz, Sabrina; Weegels, Peter; Shewry, Peter; Zevallos, Victor; Masci, Stefania; Sorrells, Mark; Gregorini, Armando; Colomba, Mariastella; Jonkers, Daisy; Huang, Xin; De Giorgio, Roberto; Caio, Giacomo P.; D'Amico, Stefano; Larre, Colette; Brouns, Fred (2022)
    Amylase/trypsin inhibitors (ATIs) are widely consumed in cereal-based foods and have been implicated in adverse reactions to wheat exposure, such as respiratory and food allergy, and intestinal responses associated with coeliac disease and non-coeliac wheat sensitivity. ATIs occur in multiple isoforms which differ in the amounts present in different types of wheat (including ancient and modern ones). Measuring ATIs and their isoforms is an analytical challenge as is their isolation for use in studies addressing their potential effects on the human body. ATI isoforms differ in their spectrum of bioactive effects in the human gastrointestinal (GI), which may include enzyme inhibition, inflammation and immune responses and of which much is not known. Similarly, although modifications during food processing (exposure to heat, moisture, salt, acid, fermentation) may affect their structure and activity as shown in vitro, it is important to relate these changes to effects that may present in the GI tract. Finally, much of our knowledge of their potential biological effects is based on studies in vitro and in animal models. Validation by human studies using processed foods as commonly consumed is warranted. We conclude that more detailed understanding of these factors may allow the effects of ATIs on human health to be better understood and when possible, to be ameliorated, for example by innovative food processing. We therefore review in short our current knowledge of these proteins, focusing on features which relate to their biological activity and identifying gaps in our knowledge and research priorities.