| 1. |
- Cossarizza, A., et al.
(författare)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Cardell, L O, et al.
(författare)
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Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1301-8
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Ekman, A. -K., et al.
(författare)
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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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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 159:1, s. 6-14
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Hellkvist, L., et al.
(författare)
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High dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase
- 2022
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:3, s. 883-96
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Henmyr, Viktor, et al.
(författare)
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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Hjalmarsson, E, et al.
(författare)
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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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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; , s. 0-
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Tidskriftsartikel (refereegranskat)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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| 11. |
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| 13. |
- 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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| 14. |
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| 15. |
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| 17. |
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| 18. |
- Pullerits, Teet, 1967, et al.
(författare)
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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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Ingår i: Clinical and experimental allergy. - 0954-7894. ; 30:10, s. 1469-75
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Song, J., et al.
(författare)
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Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 110:31
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Tidskriftsartikel (refereegranskat)abstract
- We describe a unique extracellular matrix (ECM) niche in the spleen, the marginal zone (MZ), characterized by the basement membrane glycoproteins, laminin alpha 5 and agrin, that promotes formation of a specialized population of MZ B lymphocytes that respond rapidly to blood-borne antigens. Mice with reduced laminin alpha 5 expression show reduced MZ B cells and increased numbers of newly formed (NF) transitional B cells that migrate from the bone marrow, without changes in other immune or stromal cell compartments. Transient integrin alpha 6 beta 1-mediated interaction of NF B cells with laminin alpha 5 in the MZ supports the MZ B-cell population, their long-term survival, and antibody response. Data suggest that the unique 3D structure and biochemical composition of the ECM of lymphoid organs impacts on immune cell fate.
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| 20. |
- Song, J., et al.
(författare)
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The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation
- 2023
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Ingår i: iScience. - 2589-0042. ; 26:5
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Tidskriftsartikel (refereegranskat)abstract
- Germinal center (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fiber (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrecb(high) CCL19(low)gp38(low) fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin alpha 5 (pdgfrb-cre:Lama5(fl/fl)), pre-Tfh-cells, B-cells and DCs are displaced from follicle borders, correlating with fewer Tfh-cells and GC B-cells. Total DCs are not altered in pdgfrb-cre: Lama5(fl/fl) mice, but cDC2s, which localize to laminin alpha 5 in RFs at follicle borders, are reduced. In addition, PDGFrecb(high)CCL19(low)gp38(low) FRCs show lower Ch25h expression, required for 7 alpha,25-dihydroxycholesterol synthesis that attracts pre-Tfh-cells, B-cells and DCs to follicle borders. We propose that RF basement membrane components represent a type of tissue memory that guides the localization and differentiation of both specialized FRC and DC populations, required for normal lymph node function.
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| 21. |
- Tatituri, R. V. V., et al.
(författare)
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Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs
- 2013
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:5, s. 1827-1832
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V alpha 14J alpha 18(+) invariant NKT (iNKT) cells that recognize the prototypical alpha-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) alpha-and beta-chains, does not recognize alpha-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.
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| 22. |
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| 23. |
- Albutti, A., et al.
(författare)
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Type II NKT cell agonist, sulfatide, is an effective adjuvant for oral heat-killed cholera vaccines
- 2021
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Oral vaccination has the potential to offer a safer and more efficacious approach for protection against enteric pathogens than injection-based approaches, especially in developing countries. One key advantage is the potential to induce intestinal immune responses in addition to systemic immunity. In general, antigen delivery via the oral route triggers weak immune responses or immunological tolerance. The effectiveness of oral vaccination can be improved by co-administering adjuvants. However, a major challenge is the absence of potent and safe oral adjuvants for clinical application. Here, the Type II NKT cell activator sulfatide is shown for the first time to be an effective oral adjuvant for Vibrio cholerae vaccine antigens in a mouse model. Specifically, administration of sulfatide with the oral cholera vaccine Dukoral® resulted in enhancement of intestinal antigen-specific IgA in addition to Th1 and Th17 immune responses. In summary, sulfatide is a promising adjuvant for inclusion in an oral cholera vaccine and our data further support the potential of adjuvants targeting NKT cells in new vaccine strategies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 29. |
- Bachert, C., et al.
(författare)
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Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GA(2)LEN study
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:4, s. 520-533
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Forskningsöversikt (refereegranskat)abstract
- Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA(2)LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.
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| 30. |
- Backer, V., et al.
(författare)
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Multidisciplinary approaches to identifying and managing global airways disease: Expert recommendations based on qualitative discussions
- 2023
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Ingår i: Frontiers in Allergy. - : Frontiers Media SA. - 2673-6101. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently co-exist and share pathologic features. Taking a "global" treatment approach benefits diagnosis and treatment of both, but care is often siloed by specialty: joined-up clinics are uncommon. Our objectives were to explore expert opinion to give practical suggestions to identify adults needing global airways care; enhance cross-specialty working; and widen knowledge to support diagnosis and management, integrate with existing care pathways, and supplement existing guidelines.MethodsSixteen practicing physicians from northern Europe were invited for their national and/or international standing in treating asthma and/or chronic rhinosinusitis. Appreciative Inquiry techniques were used to guide their discussions.ResultsKey themes arising were screening and referral, collaboration on management, awareness and education, and research. Provided are screening criteria and suggestions for specialist referrals, and pointers for physicians to optimize their knowledge of global airways disease. Collaborative working is underscored, and practical suggestions are given for multidisciplinary teamworking within global airways clinics. Research gaps are identified.ConclusionThis initiative provides practical suggestions for optimizing the care of adults with CRSwNP and asthma. Discussion of the role of allergy and drug exacerbations on these conditions, and care for patients with other global airways diseases were beyond scope; however, we expect some principles of our discussion will likely benefit patients with related conditions. The suggestions bridge asthma and CRSwNP management guidelines, envisioning interdisciplinary, global airway clinics relevant to various clinical settings. They highlight the value of joint screening for early recognition and referral of patients.
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| 31. |
- Benson, Mikael, 1954, et al.
(författare)
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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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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1286-91
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Tidskriftsartikel (refereegranskat)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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| 33. |
- Benson, Mikael, 1954, et al.
(författare)
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Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis
- 2005
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Ingår i: Clin Exp Allergy. - : Wiley. ; 35:4, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.
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| 34. |
- Bryborn, M., et al.
(författare)
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CLC- a novel susceptibility gene for allergic rhinitis?
- 2010
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:2, s. 220-228
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Tidskriftsartikel (refereegranskat)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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| 35. |
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| 36. |
- Clark, K., et al.
(författare)
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Structure-Function Implications of the Ability of Monoclonal Antibodies Against alpha-Galactosylceramide-CD1d Complex to Recognize beta-Mannosylceramide Presentation by CD1d
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- iNKT cells are CD1d-restricted T cells recognizing lipid antigens. The prototypic iNKT cell-agonist alpha-galactosylceramide (alpha-GalCer) alongside compounds with similar structures induces robust proliferation and cytokine production of iNKT cells and protects against cancer in vivo. Monoclonal antibodies (mAbs) that detect CD1d-alpha-GalCer complexes have provided critical information for understanding of antigen presentation of iNKT cell agonists. Although most iNKT cell agonists with antitumor properties are alpha-linked glycosphingolipids that can be detected by anti-CD1d-alpha-GalCer mAbs, beta-ManCer, a glycolipid with a beta-linkage, induces strong antitumor immunity via mechanisms distinct from those of alpha-GalCer. In this study, we unexpectedly discovered that anti-CD1d-alpha-GalCer mAbs directly recognized beta-ManCer-CD1d complexes and could inhibit beta-ManCer stimulation of iNKT cells. The binding of anti-CD1d-alpha-GalCer mAb with beta-ManCer-CD1d complexes was also confirmed by plasmon resonance and could not be explained by alpha-anomer contamination. The binding of anti-CD1d-alpha-GalCer mAb was also observed with CD1d loaded with another beta-linked glycosylceramide, beta-GalCer (C26:0). Detection with anti-CD1d-alpha-GalCer mAbs indicates that the interface of the beta-ManCer-CD1d complex exposed to the iNKT cell TCR can assume a structure like that of CD1d-alpha-GalCer, despite its disparate carbohydrate structure. These results suggest that certain beta-linked monoglycosylceramides can assume a structural display similar to that of CD1d-alpha-GalCer and that the data based on anti-CD1d-alpha-GalCer binding should be interpreted with caution.
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| 44. |
- Gudnadottir, Gunnhildur, et al.
(författare)
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Healthcare provider contact for children with symptoms of sleep-disordered breathing: a population survey.
- 2016
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Ingår i: The Journal of laryngology and otology. - 1748-5460. ; 130:3, s. 296-301
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Tidskriftsartikel (refereegranskat)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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| 45. |
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| 46. |
- Hellgren, Johan, 1965, et al.
(författare)
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Allergic rhinitis and the common cold--high cost to society.
- 2010
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 65:6, s. 776-83
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Tidskriftsartikel (refereegranskat)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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| 47. |
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| 48. |
- Henmyr, Viktor, et al.
(författare)
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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
- 2015
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)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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| 49. |
- Henmyr, V., et al.
(författare)
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Genetic variation of the Toll-like receptors in a Swedish allergic rhinitis case population
- 2017
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 18:1
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Tidskriftsartikel (refereegranskat)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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| 50. |
- Hjalmarsson, E, et al.
(författare)
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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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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 33:5, s. 362-372
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Tidskriftsartikel (refereegranskat)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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