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- Bachert, C., et al.
(author)
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Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GA(2)LEN study
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:4, s. 520-533
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Research review (peer-reviewed)abstract
- Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA(2)LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.
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| 2. |
- Bousquet, J, et al.
(author)
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GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma 'epidemic'.
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:7, s. 969-77
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Journal article (peer-reviewed)abstract
- Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA(2)LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan-European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA(2)LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project-related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA(2)LEN are reported in this paper.
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| 3. |
- Thunberg, Sarah, 1976-, et al.
(author)
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Immune regulation by CD4(+)CD25(+) T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls
- 2007
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 37:8, s. 1127-1136
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Journal article (peer-reviewed)abstract
- CD4(+)CD25(+) regulatory T (Treg) cells and the cytokines IL-10 or TGF-beta play key roles in the maintenance of T cell homeostasis and tolerance to infectious and non-infectious antigens such as allergens. To investigate the regulation of immune responses to birch pollen allergen compared with influenza antigen by Treg cells obtained from birch pollen-allergic patients and non-allergic controls. Peripheral blood was collected from 10 birch pollen-allergic patients and 10 non-allergic healthy controls. CD4(+)CD25(+) and CD4(+)CD25(-) cells isolated by magnetic-activated cell sorting were co-cultured and stimulated with birch pollen extract or influenza vaccine in the absence or presence of anti-IL-10 or soluble TGF-beta RII. CD4(+)CD25(+) cells from non-allergic controls were able to suppress influenza antigen and birch pollen stimulated effector cell proliferation, whereas CD4(+)CD25(+) cells from allergic patients suppressed influenza antigen-, but not birch pollen-stimulated proliferation. The production of Th1 cytokines, but not Th2 cytokines, was suppressed by CD4(+)CD25(+) cells from both allergic patients and controls, upon stimulation with birch pollen extract. Neutralization of IL-10 led to significantly increased production of IFN-gamma in cultures with CD4(+)CD25(-) T effector cells. In addition, six-fold higher concentrations of TNF-alpha were detected after neutralization of IL-10 in both CD4(+)CD25(-) and CD4(+)CD25(+) cell cultures from allergic patients and controls. We demonstrate that the allergen-specific suppressive function of CD4(+)CD25(+) cells from allergic patients is impaired compared with non-allergic controls. Moreover, neutralization of IL-10 enhances the production of TNF-alpha, suggesting counter-acting properties of IL-10 and TNF-alpha, where IL-10 promotes tolerance and suppression by Treg cells and TNF-alpha promotes inflammatory responses.
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| 7. |
- Gafvelin, G, et al.
(author)
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Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1
- 2005
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 138:1, s. 59-66
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Journal article (peer-reviewed)abstract
- Background: Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients. Methods: Blood was drawn from patients of the Swedish centre (n=27; rBet v 1 fragments: n=10; rBet v 1 trimer: n=8, and placebo-aluminium hydroxide: n=9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study. Results: Bet v 1-specific IgG levels, consisting of IgG 1, IgG 2 and IgG 4, were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p<0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p=0.07) and an increase of IL-12-producing (p=0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment. Conclusion: Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative. Copyright (C) 2005 S. Karger AG, Basel.
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