| 1. |
- Andelid, Kristina, 1953, et al.
(författare)
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Myeloperoxidase as a marker of increasing systemic inflammation in smokers without severe airway symptoms
- 2007
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Ingår i: Respiratory medicine. - : Elsevier BV. - 0954-6111. ; 101:5, s. 888-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is increasing evidence of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD), but there is very little information on the development of systemic inflammation in smokers without severe airway symptoms. In this longitudinal study, we examined whether smokers with mild or no airway symptoms develop signs of systemic inflammation by assessing inflammatory markers in blood over a 6-year period. METHODS: Forty smokers and 28 male never-smokers were investigated in 1995 (year 0) and 6 years later (year 6). At year 6, 11 smokers had stopped smoking (quitters); these subjects were analysed as a separate group. At year 0 and 6, we measured serum levels of myeloperoxidase (MPO), lysozyme and human neutrophil lipocalin (HNL), regarded as markers of activity in neutrophils plus monocyte-lineage cells, monocyte-lineage cells only and neutrophils only. RESULTS: All systemic markers of inflammation (MPO, HNL and lysozyme) were significantly higher in smokers than in never smokers at year 6. For MPO alone, smokers only displayed a unique pattern compared with the other groups; the concentration of MPO in blood increased among smokers during the 6-year period, and this increase was statistically significant compared with that observed in never-smokers. Even though quitters did not display any clear change in MPO, we observed a statistically significant negative correlation between the change in blood MPO and the duration of smoking cessation in this group. For HNL and lysozyme, the changes over time were similar in smokers and never-smokers, with no statistically significant difference compared with quitters. CONCLUSION: This study provides evidence that male smokers without severe airway symptoms develop an increasing systemic inflammation during a 6-year period. The study forwards both direct and indirect evidence that MPO may be an early marker of this systemic inflammation. However, our study also forwards indirect evidence that ongoing tobacco smoking may "drive" the level of systemic HNL and lysozyme. The origin of the increased MPO and its value as an easily measured predictor for future COPD deserves to be further evaluated.
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| 2. |
- Arvidsson, Monica, 1955, et al.
(författare)
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Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study
- 2004
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Ingår i: Allergy. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few placebo-controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo-controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients. METHODS: Nineteen patients with a history of birch-pollen-induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment. RESULTS: All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty-four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group. CONCLUSION: Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti-inflammatory effect of the treatment.
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| 3. |
- Arvidsson, Monica, 1955, et al.
(författare)
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Early and late phase asthmatic response in lower airways of cat-allergic asthmatic patients - a comparison between experimental and environmental allergen challenge
- 2007
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Ingår i: Allergy. - 0105-4538. ; 62:5, s. 488-94
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Tidskriftsartikel (refereegranskat)abstract
- Background: Standardized experimental allergen challenges are usually adopted to investigate the effect of allergen exposure on the lower airways. Environmental (natural) allergen challenges are used less often, mainly because of difficulties in standardizing the method, safety reasons and costs. The aim of this study was to investigate the relationship between an experimental and an environmental bronchial challenge. For this reason a natural challenge model was developed. Methods: Sixty-two patients with a history of cat allergen-induced symptoms involving the lower airways, positive skin prick test, positive in vitro specific IgE to cat allergen and bronchial hyper-responsiveness were included. All 62 patients underwent an experimental challenge in the laboratory followed by an environmental allergen challenge. Results: All 62 patients developed an early asthmatic response [>/=20% fall in forced expiratory volume in 1 s (FEV(1))] in the experimental challenge and 60% (37/62) during the environmental challenge. A late asthmatic response (>/=15% fall in FEV(1) within 3-24 h) was seen in 56% (35/62) of the patients after the experimental challenge. Following the environmental challenge 47% (29/62) of the patients developed a late response. Thirty-four per cent (21/62) of the patients developed a late response in both challenge models and 31% (19/62) did not develop a late response in any model. Thus, there was consistency in 65% (40/62) of the patients in both challenge models. Conclusion: We found consistency in the pattern of response to inhaled allergen between the two challenge models and we believe that experimental bronchial challenge is likely to reflect the development of relevant inflammation in the lower airways after low-dose allergen exposure in the environment.
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| 4. |
- Arvidsson, Monica, 1955, et al.
(författare)
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Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy
- 2002
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Ingår i: J Allergy Clin Immunol. ; 109:5 Pt 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Birch pollen is a common allergen in northern, central, and eastern Europe. Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal. Long-term, placebo-controlled studies with subcutaneously administered standardized birch pollen extract are lacking. OBJECTIVE: The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen-allergic patients in a double-blind, placebo-controlled trial. METHODS: Forty-nine patients with histories of birch pollen allergy from the upper and lower airways, positive skin prick test and conjunctival provocation test results, and in vitro specific IgE to birch pollen (Betula verrucosa ) extract were included. Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind, randomized, placebo-controlled study. Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season. RESULTS: Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study. The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and 2.1 and 4.3, respectively, in the placebo group. The differences between the groups were significant (P =.05 in 1997 and P =.005 in 1998). The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group (P =.004 for 1997 and P =.004 for 1998). CONCLUSION: Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen-allergic patients during the pollen season.
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| 5. |
- Calderon, Moises A, et al.
(författare)
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EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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| 6. |
- Dahl, R., et al.
(författare)
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Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis
- 2006
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Ingår i: J Allergy Clin Immunol.. ; 118:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. OBJECTIVE: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abello, Horsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. RESULTS: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.
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| 7. |
- Dahl, R., et al.
(författare)
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Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis
- 2006
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Ingår i: Allergy.. ; 61:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75 000 SQ-T (Grazax((R))Phleum pratense, ALK-Abello) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis. Methods: A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc. Results: Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 mug) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002). Conclusions: Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.
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| 8. |
- Dahl, Ronald, et al.
(författare)
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Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years.
- 2008
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 121:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abell? A/S, H?rsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. OBJECTIVE: We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. METHODS: The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. RESULTS: The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment. CONCLUSION: Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment.
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| 9. |
- de Monchy, J., et al.
(författare)
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Living & learning with allergy: a European perception study on respiratory allergic disorders
- 2004
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Ingår i: Respir Med. ; 98:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Knowledge of allergy patients' perception of own disease is inadequate, and understanding of the impact of local environment, including family and health-care system, on patients' management of disease is insufficient. We examined the potential of telephone-based survey techniques for establishing this knowledge in 10 European countries. METHODS: A two-phased questionnaire developed by use of focus groups in seven countries was translated into 10 languages. To ensure that the true values of the populations were restored in randomly selected populations, 75,343 telephone numbers selected for screening represented balanced national distributions of households. RESULTS: Eight thousand two hundred and sixty-eight respiratory allergy sufferers were identified by the telephone screening process. 85.4% accepted to participate in the survey and 89.6% completed both phases comprising 34 questions and rating of 49 statements. Data for each country were weighted in terms of age, sex and the recorded allergy prevalence within age intervals. CONCLUSIONS: The telephone survey technique allowed for establishment of random representative samples, and application of mathematical weighting procedures assured that the true national values were restored in the data set. As all interviews were performed in a standardised manner we conclude that the telephone-based survey methodology enables national representative data set to be established and compared.
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| 10. |
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| 11. |
- Durham, S. R., et al.
(författare)
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Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis
- 2006
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Ingår i: J Allergy Clin Immunol.. ; 117:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. OBJECTIVE: To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. METHODS: A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abello, Horsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. RESULTS: Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. CONCLUSION: This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. CLINICAL IMPLICATIONS: For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.
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| 12. |
- Everberg, Henrik, et al.
(författare)
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Aqueous two-phase partitioning for proteomic monitoring of cell surface biomarkers in human peripheral blood mononuclear cells
- 2006
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 5:5, s. 1168-75.
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Tidskriftsartikel (refereegranskat)abstract
- For proteomic monitoring of processes such as allergy or inflammation an efficient pre-fractionation strategy is required. We isolated plasma membranes from human peripheral blood mononuclear (PBM) cells by aqueous two-phase partitioning. After 1DE combined with LC-MS/MS, several cell surface marker proteins and in total 60 different plasma membrane proteins (out of 84 identified proteins, i.e., 72%) were detected. Plasma membranes obtained were from only one human donor, the procedure is therefore applicable for individual patient screening.
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| 13. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season
- 2004
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Ingår i: Clin Exp Allergy. ; 34:9, s. 1364-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CD4(+)CD25+ regulatory T cells suppress proliferation and cytokine production by human T cells both to self-antigens and exogenous antigens. Absence of these cells in human newborns leads to multiple autoimmune and inflammatory disorders together with elevated IgE levels. However, their role in human allergic disease is still unclear. OBJECTIVE: This study aimed to evaluate the capacity of CD4(+)CD25+ regulatory T cells to suppress proliferation and cytokine production outside and during birch-pollen season in birch-allergic patients relative to non-allergic controls. METHODS: CD4+ cells were obtained from blood of 13 birch-allergic patients and six non-allergic controls outside pollen season and from 10 birch-allergic patients and 10 non-allergic controls during birch-pollen season. CD25+ and CD25- fractions were purified with magnetic beads and cell fractions, alone or together in various ratios, were cultured with antigen-presenting cells and birch-pollen extract or anti-CD3 antibody. Proliferation and levels of IFN-gamma, IL-13, IL-5 and IL-10 were measured by thymidin incorporation and ELISA, respectively. Numbers of CD25+ cells were analysed by flow cytometry. RESULTS: CD4(+)CD25+ regulatory T cells from both allergics and non-allergics potently suppressed T cell proliferation to birch allergen both outside and during birch-pollen season. However, during season CD4(+)CD25+ regulatory T cells from allergic patients but not from non-allergic controls were defective in down-regulating birch pollen induced IL-13 and IL-5 production, while their capacity to suppress IFN-gamma production was retained. In contrast, outside pollen season the regulatory cells of both allergics and non-allergic controls were able to inhibit T-helper 2 cytokine production. CONCLUSION: This is the first study to show differential suppression of Th1 and Th2 cytokines, with CD4(+)CD25+ regulatory T cells from birch-pollen-allergic patients being unable to down-regulate Th2, but not Th1 responses during birch-pollen season.
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| 14. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Specific Immunotherapy to Birch Allergen Does not Enhance Suppression of Th2 Cells by CD4(+)CD25 (+) Regulatory T Cells During Pollen Season.
- 2009
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 29:6, s. 752-60
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to investigate the suppressive capacity of CD25(+) regulatory T cells on birch allergen-induced T-cell responses during the first birch pollen season after initiation of specific immunotherapy (SIT). METHODS: CD25(pos) and CD25(neg) T cells were purified from blood of birch-allergic SIT patients and birch-allergic controls, stimulated with birch pollen extract, and analyzed for T-cell proliferation and production of interferon gamma (IFN-gamma), interleukin (IL)-5 and IL-10. RESULTS: We show that allergen-induced proliferation and IFN-gamma production were suppressed equally well by CD25(pos) T cells from SIT patients and controls, while the IL-5 production was not suppressed by either of the groups. IL-10 levels were higher in SIT patients relative to controls only when CD25(neg) and CD25(pos) were cultured together. Furthermore, neither FOXP3 levels nor proportions of CD25(high) T cells were enhanced in SIT patients compared to allergic controls. DISCUSSION: These results suggest that the Th2-suppressive capacity of allergen-stimulated CD25(pos) Treg in vitro is not improved by SIT in spite of increased IL-10 production from T cells.
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| 15. |
- Hedlin, Gunilla, et al.
(författare)
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Immunmodulerande behandling
- 2009
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Ingår i: Allergi och astma. Hedlin G & Larsson K, red. Studentlitteratur. - 9789144029962 ; , s. 287-300
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 16. |
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| 17. |
- Malm-Erjefält, M., et al.
(författare)
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Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation
- 2005
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Ingår i: Clin Exp Allergy. ; 35:10
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Tidskriftsartikel (refereegranskat)abstract
- Summary Background In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. Objective To determine the degranulation status of circulating eosinophils in common allergic diseases. Methods Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. Results Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). Conclusion In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.
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| 18. |
- Mascarell, L., et al.
(författare)
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Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells
- 2015
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Ingår i: Allergy. - : Wiley. - 0105-4538. ; 70:4, s. 408-419
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Tidskriftsartikel (refereegranskat)abstract
- Background: A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. Methods: Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). Results: Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207(+) Langerhans cells (LCs) and CD11c(+) myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68(+) macrophages, CD117(+) mast cells, and CD4(+)/CD8(+) T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207(+) LCs found in oral tissues from patients with OAS, when compared to OAS(-) patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE(+) cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68(+) macrophages located in the LP, and to a lesser extent CD207(+) LCs in the epithelium. Conclusion: Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207(+) LCs possibly involved in the physiopathology of OAS and (ii) CD68(+) macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT.
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| 19. |
- Pauli, Gabrielle, et al.
(författare)
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Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis.
- 2008
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 122:5, s. 951-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years. RESULTS: Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities (P < .0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels, which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were observed in the rBet v 1-treated group. CONCLUSION: The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.
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| 20. |
- Plewako, Halina, 1972, et al.
(författare)
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A follow-up study of immunotherapy-treated birch-allergic patients: effect on the expression of chemokines in the nasal mucosa
- 2008
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 38:7, s. 1124-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Specific immunotherapy (SIT) is the only treatment producing lasting clinical improvement in patients with allergy. We investigated the long-term effect of SIT treatment on the expression of chemokines: eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted) and thymus and activation-regulated chemokine (TARC), and their receptors CCR3 and CCR4 in biopsies of nasal mucosa from birch-allergic individuals. Methods Sixteen patients who completed a 3-year treatment programme 3-5 years ago, and 12 untreated, matched controls were included in the study. Patients recorded symptoms and use of rescue medication before and during the pollen season. Nasal mucosa samples obtained before and during the season were stained for eosinophil and mast cell markers and for eotaxin, RANTES, TARC, CCR3 and CCR4. Results During the pollen season, rhinoconjunctivitis symptoms increased in both SIT and control groups (P =0.001 and 0.002, respectively). However, SIT patients had 37% fewer symptoms than controls. Medication use increased in both groups (P =0.002) during the season but the SIT group used 28% less than the controls (P =0.02). The number of eosinophils in the nasal mucosa increased in the control group (P= 0.01) and the difference between the groups was significant during the season (P =0.01). No seasonal increase in the numbers of mast cells was seen, but during the pollen season, more (P =0.02) AA+ cells were found in the controls than in the SIT group. The number of eotaxin1 and RANTE+ cells increased in the control group (P= 0.01 and 0.03, respectively) and the difference between groups during the season was significant (P =0.01 and 0.01, respectively). The TARC+ cell numbers were lower in the SIT group during the season (P =0.003). The CCR3+ cells increased only in the control group during the pollen season and remained unchanged in SIT patients, while CCR4+ cell numbers increased in both the control (P = 0.03) and SIT (P = 0.02) groups. Conclusion This study confirmed that decreased numbers of eosinophils in the nasal mucosa is a long-lasting effect of birch SIT. SIT also prevented seasonal rises in the number of cells expressing the chemokines eotaxin and RANTES
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| 21. |
- Plewako, Halina, 1972, et al.
(författare)
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Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy
- 2006
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 141:4, s. 346-353.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies using rush immunotherapy (RIT) have shown that rapid protection can be achieved using protocols allowing a fast increment of allergen dose. We examined the early effects of RIT on basophil numbers and expression of CD203c, production of interleukin (IL)-4 and IL-13 and histamine release by basophils in the peripheral blood of patients treated with immunotherapy and controls. Methods: Twelve patients treated with RIT and 4 untreated controls were included in the study. Any adverse events were evaluated during the incremental phase of RIT. Mononuclear cells were isolated before the start of RIT and 3 days, I week, 4 weeks and 3 months after the beginning of the treatment. Histamine release upon allergen stimulation, expression of CD203c and allergen-induced production of IL-4 and IL-13 by basophils were examined. Results: Significant decreases in blood basophil count (p = 0.02) were observed early in the treatment, returning to baseline values 1 week after the start of RIT. Similarly, histamine release decreased at day 3 (p = 0.02), but returned to pretreatment levels after I week. Also, the percentage of IL-4+ and IL-13+ basophils and levels of CD203c expression were markedly reduced early in the treatment. IL-4 and IL-13 production correlated with histamine release and CD203c expression. Histamine release and production of IL-4 and IL-13 by basophils before the treatment correlated with the severity of adverse events during the incremental phase of RIT. Conclusion: We report the decrease in blood basophil numbers, their lower activation status and the reduced production of IL-4 and IL-13 early in the course of RIT. This early suppression of basophil activation could be one mechanism behind the protective effect of RIT.
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| 22. |
- Plewako, Halina, 1972, et al.
(författare)
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Increased expression of lipoxygenase enzymes during pollen season in nasal biopsies of pollen-allergic patients
- 2006
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Ingår i: Allergy. ; 61:6, s. 725-30
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure of patients sensitized to pollen triggers development of seasonal allergic rhinitis symptoms (SAR). Eicosanoids are a group of arachidonic acid metabolites contributing to the symptoms of SAR. The aim of this study was to investigate seasonal changes in the expression of enzymes of the eicosanoid pathway in the nasal mucosa of patients with SAR. Methods: Twenty SAR patients allergic to birch or grass and eight healthy subjects were included in the study. Patients registered rhinoconjunctivitis symptoms and use of rescue medication before and during the pollen season. Nasal biopsies were obtained before and around the peak of the season, sectioned and stained using markers for eosinophils, mast cells, T cells and neutrophils. Antibodies against the following enzymes were also used: cyclo-oxygenase (COX-1, COX-2), 5-lipoxygenase (5-LO), 5-lipoxygenase-activating factor (FLAP), LTA(4) hydrolase (LTA(4)h) and LTC(4) synthase (LTC(4)s). Results: During the pollen season symptoms of rhinoconjunctivitis and medication score increased significantly (P = 0.001; P = 0.001 respectively). During the pollen season numbers of eosinophils (P = 0.02) and cell positive 5-LO (P = 0.02), LTC(4)s (P = 0.04) and LTA(4)h (P = 0.02) increased significantly. During season number of mast cells and cells expressing 5-LO and LTA(4)h were higher in SAR than in healthy controls group (P = 0.02; P = 0.01; P = 0.03 respectively). Conclusion: In sensitized patients exposure to pollen allergen results in increased expression of enzymes of the eicosanoid pathway.
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| 23. |
- Plewako, Halina, 1972, et al.
(författare)
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The effect of specific immunotherapy on the expression of costimulatory molecules in late phase reaction of the skin in allergic patients
- 2004
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Ingår i: Clin Exp Allergy. - : Wiley. ; 34:12, s. 1862-1867
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Tidskriftsartikel (refereegranskat)abstract
- Background Specific immunotherapy (SIT) modulates immune responses to allergens resulting in improvement of allergic symptoms. However, the mechanisms behind the clinical changes are not clear. Participation of costimulatory molecules on antigen-presenting cells and T cells in the process of antigen recognition is suggested to be of essential importance. The SIT effect on expression of costimulatory molecules has not been earlier examined. Methods Forty-one birch-allergic patients were treated with SIT or placebo. After 1 year of treatment skin biopsies were obtained 24 h following allergen challenge. Sections were stained with antibodies against: EG2 (eosinophils), CD4 (T cells), CD68 (macrophages), CD1a (Langerhans cells), CD28 (on T cells) and costimulatory molecules (CD80, CD86). Results Following allergen challenge number of the CD4+ and CD68+ cells increased significantly (P=0.002, 0.0001, respectively) in the placebo, but not in the SIT-treated patients. The difference between groups was significant (P=0.003, 0.01, respectively). The numbers of EG2+ cells increased significantly in both groups. CD80+ cell numbers increased in the placebo (P=0.01) but not in the SIT group. The number of CD86+ cells increased in both groups (placebo, P=0.001; SIT, P=0.01) but significantly less in the SIT group (P=0.05). The numbers of CD28+ cells increased in the placebo (P=0.001) but remained unchanged in the SIT group. The difference between the groups was significant (P=0.05). Conclusion There were lower numbers of cells expressing costimulatory molecules in SIT-treated than in placebo-treated patients. Decreased costimulation may lead to diminished immune response following allergen exposure. This could be an important factor contributing to the clinical improvement after SIT.
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| 24. |
- Rak, Sabina, 1945, et al.
(författare)
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Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy
- 2005
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Ingår i: Allergy. ; 60:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Specific allergen immunotherapy (SIT) and nasal steroids (NS) are considered effective anti-inflammatory treatments for allergic rhinitis, although their mechanism of action differs. Objective: The aim of this study was to examine the effect of treatment with NS and SIT on different populations of inflammatory cells in the nasal mucosa and to compare cell numbers before and during the birch pollen season in patients with seasonal allergic rhinitis. Methods: In a randomized, double-blind, double dummy comparative study, 41 patients with seasonal rhinoconjunctivitis were treated with birch SIT or NS (budesonide 400 mug daily). Treatment with NS started before the birch pollen season and at the same time SIT-treated patients reached the maintenance dose. Nasal biopsies for immunohistochemistry were obtained before the season and start of the treatments and at the peak of the pollen season during treatment. Results: Symptoms of rhinoconjunctivitis increased significantly in both groups during the pollen season but less in the NS-treated group and the difference between the treatment groups was significant at the end of the season (P = 0.03). Immunohistochemistry of nasal biopsies from NS-treated patients showed significantly fewer CD1a(+), IgE(+) and FcepsilonRI(+) cells during the season compared with preseason (P = 0.02, P = 0.001 and P = 0.0004, respectively) and with seasonal values of the SIT-treated group (P = 0.002, P = 0.002 and P = 0.0004 respectively). Conclusion: Treatment with NS but not SIT decreased the numbers of CD1a(+), IgE(+) and FcepsilonRI(+) cells during the birch pollen season. Our data indicate that treatment with NS has a broader anti-inflammatory range than SIT.
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| 25. |
- Rak, Sabina, 1945, et al.
(författare)
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Once-daily sublingual allergen-specific immunotherapy improves quality of life in patients with grass pollen-induced allergic rhinoconjunctivitis: A double-blind, randomised study
- 2007
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Ingår i: Qual Life Res. - 0962-9343. ; 16:2, s. 191-201
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Tidskriftsartikel (refereegranskat)abstract
- The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX(R)) or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.
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| 26. |
- Seymour, M. L., et al.
(författare)
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Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
- 2001
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Ingår i: Am J Respir Crit Care Med. - 1073-449X. ; 164:11, s. 2051-6
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Tidskriftsartikel (refereegranskat)abstract
- Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.
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| 27. |
- Van Neerven, R., et al.
(författare)
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A double-blind, placebo-controlled birch allergy vaccination study: inhibition of CD23-mediated serum-immunoglobulin E-facilitated allergen presentation
- 2004
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Ingår i: Clin Exp Allergy. ; 34:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : The clinical efficacy of specific allergy vaccination (SAV), previously called specific immunotherapy is well documented. The working mechanism of this treatment is not completely known at present. Allergen-specific CD4+ T lymphocytes are activated at extremely low allergen concentrations in vivo possibly as a result of serum IgE-facilitated allergen presentation (S-FAP). Previously, we have shown that this process can be inhibited by long-term birch SAV sera. METHODS : In the present study, we have analysed sera from birch-allergic patients in a randomized double-blind, placebo-controlled clinical trial for their ability to mediate S-FAP. Birch-specific IgE levels were not changed after SAV. Bet v 1-specific IgE levels, however, were significantly decreased (P<0.05) and Bet v 1-specific IgG4 levels were strongly increased after SAV (P<0.001). None of these changes were observed in the placebo group. When the sera were tested for their ability to induce S-FAP, a complete abrogation of this effect was noted in the sera from patients receiving active treatment (P<0.001), but not in the control group. This inhibition of S-FAP seemed to be associated with the reduction in the ratio between Bet v 1-specific IgE and IgG4 antibodies in serum, but a clear correlation could not be demonstrated. CONCLUSION : In conclusion, the present study clearly shows that SAV leads to an inhibition of the S-FAP needed to obtain optimal T cell activation at the low allergen concentrations present in vivo. This novel mechanism may explain the increased allergen threshold levels found in allergen provocation tests and the reduction of late-phase reactions observed after SAV.
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| 28. |
- van Ree, R, et al.
(författare)
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The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification.
- 2008
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 63:3, s. 310-26
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Tidskriftsartikel (refereegranskat)abstract
- Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.
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| 29. |
- Wosinska-Becler, Katarzyna, 1972, et al.
(författare)
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Cytokine production in peripheral blood cells during and outside the pollen season in birch-allergic patients and non-allergic controls
- 2004
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Ingår i: Clin Exp Allergy. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : The naturally occurring pollen season permits observation of the kinetic changes in the process of allergic inflammation. We examined cytokine production in peripheral blood (PB) T cells and monocytes obtained from birch-allergic patients both during and outside the pollen season. METHODS : PB from 16 patients and six healthy controls was obtained during the alder pollen season, at the beginning and the peak of the birch pollen season and outside the pollen season. Mononuclear cells (MNC) were stimulated with allergen and polyclonal activators. For flow cytometric analysis, MNC were stained with monoclonal antibodies (MoAbs) against the cell surface markers CD3, CD8, CD14 and the intracellular cytokines IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN-gamma. RESULTS : In allergic patients, significant increases in clinical symptoms, use of medication, eosinophil numbers and birch-specific IgE were found during the pollen season. In vitro allergen stimulation increased the number of GM-CSF+ monocytes (P<0.01) and this increase was dependent on allergen exposure. The IL-4/IFN-gamma ratio rose (P<0.001) at the peak of birch pollen season and the ratio correlated with symptom scores during the birch season. In the CD4+ cell population, the numbers of GM-CSF+ cells were higher throughout the alder and birch seasons compared with outside the pollen season (P<0.05). No such changes were seen in the healthy controls. CONCLUSIONS : The main finding of our study was the increased percentage of GM-CSF+ monocytes in atopic subjects compared with healthy controls. In allergic patients, natural seasonal pollen exposure resulted in increased numbers of GM-CSF+ cells among both monocytes and CD4+ T cells. We have also shown that a seasonal change in Th2/Th1 cytokine ratio requires an adequate and prolonged allergen stimulation that is seen late in the pollen season.
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