| 1. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 2. |
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| 3. |
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| 4. |
- Hellkvist, L., et al.
(author)
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High dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase
- 2022
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In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:3, s. 883-96
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Journal article (peer-reviewed)abstract
- Background The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. Results Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. Conclusion Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.
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| 5. |
- Cardell, L O, et al.
(author)
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Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1301-8
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Journal article (peer-reviewed)abstract
- Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease.
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| 6. |
- Ekman, A. -K., et al.
(author)
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Systemic Up-Regulation of TLR4 Causes Lipopolysaccharide-Induced Augmentation of Nasal Cytokine Release in Allergic Rhinitis
- 2012
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 159:1, s. 6-14
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Journal article (peer-reviewed)abstract
- Background: Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release. Methods: In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed. Results: TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-gamma and TNF-alpha. Conclusion: A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release. Copyright (C) 2012 S. Karger AG, Basel
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| 7. |
- Henmyr, Viktor, et al.
(author)
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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
- 2015
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995.
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared.RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations.CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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| 8. |
- Hjalmarsson, E, et al.
(author)
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A five-year open follow up of a randomized, double-blind placebo-controlled trial of intralymphatic immunotherapy for birch and grass reveals remaining beneficial effects
- 2022
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In: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; , s. 0-
-
Journal article (peer-reviewed)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 9. |
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| 10. |
- Malm-Erjefält, M., et al.
(author)
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Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation
- 2005
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In: Clin Exp Allergy. ; 35:10
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Journal article (peer-reviewed)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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| 11. |
- Pullerits, Teet, 1967, et al.
(author)
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Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid
- 2000
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In: Clinical and experimental allergy. - 0954-7894. ; 30:10, s. 1469-75
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Journal article (peer-reviewed)abstract
- BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Benson, Mikael, 1954, et al.
(author)
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A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis.
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1286-91
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Journal article (peer-reviewed)abstract
- BACKGROUND: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. OBJECTIVE: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. METHODS: CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. RESULTS: Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. CONCLUSION: Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR.
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| 17. |
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| 18. |
- Bryborn, M., et al.
(author)
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CLC- a novel susceptibility gene for allergic rhinitis?
- 2010
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:2, s. 220-228
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Journal article (peer-reviewed)abstract
- P>Background: Studies of the nasal lavage fluid proteome have previously identified proteins differently expressed in patients with symptomatic allergic rhinitis, e.g. S100A7, prolactin-inducible protein (PIP), wingless-type MMTV integration site family, member 2B (WNT2B), Charcot-Leyden crystal protein (CLC) and palate lung nasal epithelial clone (PLUNC). The aim of the present study was to investigate if genetic variation associated with allergic rhinitis can be found in these genes. Methods: Peripheral blood was collected from 251 patients with birch and/or grass pollen-induced allergic rhinitis and 386 nonatopic healthy controls. A total of 39 single nucleotide polymorphisms (SNPs) distributed over the genes PIP, WNT2B, CLC and PLUNC were selected from dbSNP, genotyped and investigated for associations with allergic rhinitis. Twelve additional SNPs were subsequently analysed for CLC. Results: All 22 investigated SNPs in CLC were polymorphic. Ten SNPs yielded significant differences between cases and controls with respect to genotype frequencies. Homozygotes for the minor allele were more common in allergic individuals compared to healthy controls. The minor alleles of these SNPs were all located on the same haplotype. Furthermore, homozygotes for the minor allele of two of the promoter SNPs had higher average scores for birch in skin prick test. In contrast, for seven SNPs within the gene, heterozygotes and homozygotes for the major allele had higher average scores for grass. None of the other three genes showed association. Conclusion: Genetic variation in CLC was found to be associated with allergic rhinitis. The pattern of variation is compatible with a recessive inheritance model and the previously observed altered protein levels detected in patients with allergic rhinitis.
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| 19. |
- Gudnadottir, Gunnhildur, et al.
(author)
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Healthcare provider contact for children with symptoms of sleep-disordered breathing: a population survey.
- 2016
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In: The Journal of laryngology and otology. - 1748-5460. ; 130:3, s. 296-301
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Journal article (peer-reviewed)abstract
- Symptoms of sleep-disordered breathing in children, such as frequent snoring, apnoea and choking, may lead to health problems if untreated. The caregiver's level of awareness of these symptoms has been poorly studied. This study aimed to study healthcare provider contact related to sleep-disordered breathing symptoms in a population of children aged 0-11 years.
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| 20. |
- Hellgren, Johan, 1965, et al.
(author)
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Allergic rhinitis and the common cold--high cost to society.
- 2010
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:6, s. 776-83
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Journal article (peer-reviewed)abstract
- The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population.
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| 21. |
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| 22. |
- Henmyr, Viktor, et al.
(author)
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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
- 2015
-
In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995.
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations. METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared. RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations. CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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| 23. |
- Henmyr, V., et al.
(author)
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Genetic variation of the Toll-like receptors in a Swedish allergic rhinitis case population
- 2017
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF≤1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients. Methods: Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data. Results: The overall level of genetic variation was clearly different among the 10 TLR genes. The TLR10-TLR1-TLR6 locus was the most variable, while the TLR7-TLR8 locus was consistently showing a much lower level of variation. The AR patients had a total of 37 promoter polymorphisms with 14 rare (MAF≤1%) and 14 AR-specific polymorphisms. These numbers were highly similar when comparing the AR and the European part of the 1000Genomes populations, with the exception of TLR10 where a significant (P=0.00009) accumulation of polymorphisms were identified. The coding sequences had a total of 119 polymorphisms, 68 were rare and 43 were not present in the European part of the 1000Genomes population. Comparing the numbers of rare and AR-specific SNPs in the patients with the European part of the 1000Genomes population it was seen that the numbers were quite similar both for individual genes and for the sum of all 10 genes. However, TLR1, TLR5, TLR7 and TLR9 showed a significant excess of rare variants in the AR population when compared to the non-Finnish European part of ExAC. In particular the TLR1 S324*nonsense mutation was clearly overrepresented in the AR population. Conclusions: Most TLR genes showed a similar level of variation between AR patients and public databases, but a significant excess of rare variants in AR patients were detected in TLR1, TLR5, TLR7, TLR9 and TLR10. This further emphasizes the frequently reproduced TLR10-TLR1-TLR6 locus as being involved in the pathogenesis of allergic rhinitis.
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| 24. |
- Hjalmarsson, E, et al.
(author)
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A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects
- 2023
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In: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 33:5, s. 362-372
-
Journal article (peer-reviewed)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 25. |
- Hjalmarsson, E, et al.
(author)
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A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects
- 2023
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In: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 33:5, s. 363-372
-
Journal article (peer-reviewed)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 26. |
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| 27. |
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| 28. |
- Nilsson, D., et al.
(author)
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Replication of genomewide associations with allergic sensitization And allergic rhinitis
- 2014
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 69:11, s. 1506-1514
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Journal article (peer-reviewed)abstract
- Background: Three genomewide metastudies have recently reported associations with self-reported allergic rhinitis and allergic sensitization. The three studies together identified a set of 37 loci but showed low concordance. This study investigates the reproducibility of the detected single nucleotide polymorphism (SNP) associations in an extensively characterized longitudinal cohort, BAMSE. Methods: Phenotypic evaluation of allergic rhinitis (AR) and allergic sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age. Allele frequencies of 39 SNPs were investigated for association with the exact allergic phenotypes of the metastudies. Odds ratios and false discovery rates were calculated, and the impact of asthma was evaluated. The cases were also evaluated for age at onset effects ( <= or >8 years of age). Results: Association tests of the 39 SNPs identified 12 SNPs with P-values <0.05 and Q-values <0.10. Two of the four loci (TLR6-TLR1 and HLA-DQA1-HLA-DQB1) identified in all three original studies were also identified in this study. Three SNPs located in the TLR6-TLR1 locus had the lowest P-values and Q-values <0.1 when using a well-defined AR phenotype. Two loci showed significant age at onset effects, but the effect of asthma on the associations was very limited. Conclusion: The TLR6-TLR1 locus is likely to have a central role in the development of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis.
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| 29. |
- Stålenheim, Gunnemar, et al.
(author)
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The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair (R)) treatment
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:10, s. 1472-1477
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Journal article (peer-reviewed)abstract
- Background: Some patients with allergic asthma treated with anti-IgE (Xolair (R)) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair (R). Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). Methods: In a double-blind placebo controlled trial 20 patients with a high (> 3.8%) and 18 with a low (< 1%) percentage of IgE antibodies to cat were given Xolair (R) for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. Results: The CD-sens dropped significantly in both the high (P < 0.001) and low (P < 0.001) group on Xolair (R) but did not change significantly after placebo. For Xolair (R)-treated patients, at the end of the trial there was a highly significant (P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. Conclusions: The currently recommended doses of Xolair (R) very efficiently eliminate IgE antibodies if the IgE antibody fraction is < 1% of total IgE but has not enough effect on allergen sensitivity if the fraction is > 3-4%. Further studies will show if increased doses of Xolair (R) would help also these patients, who seem to represent about 1/3 of the patient population.
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| 30. |
- Tengroth, L, et al.
(author)
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Activation of Activin receptor-like kinases curbs mucosal inflammation and proliferation in chronic rhinosinusitis with nasal polyps
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 1561-
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Journal article (peer-reviewed)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing obstruction of the nasal cavity. Its cause remains unclear. The transforming growth-factor beta (TGF-β) superfamily and their receptors, termed Activin receptor-like kinases (ALKs), have recently been suggested to play a role in local airway inflammation, but have so far not been evaluated in human nasal epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1–7 were expressed in the nasal polyp epithelium, and the expression of ALK1-6 was markedly elevated in polyps compared to nasal mucosa from healthy controls. Stimulation with the ALK ligand TGF-β1 decreased Ki67 expression in HNECs from CRSwNP patients, not evident in controls. Likewise, TGF-β1, Activin A and Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre-stimulation with TGF-β1, Activin A, BMP4 and Activin B attenuated a TNF-α-induced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls. In conclusion, an increased expression of ALK1-6 was found on polyp epithelial cells and ligand stimulation appeared to reduce proliferation and local inflammation in polyps.
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| 31. |
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| 32. |
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| 33. |
- Tomassen, P., et al.
(author)
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Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis - a GA2LEN study
- 2011
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 66:4, s. 556-561
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Journal article (peer-reviewed)abstract
- Background: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA2LEN European survey. Methods: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. Results: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I2 = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Conclusion: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.
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