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- 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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- Bousquet, J, et al.
(författare)
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Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial
- 2005
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 35:6, s. 723-727
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Tidskriftsartikel (refereegranskat)abstract
- Background Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled. fluticasone. Methods A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (IMPACT: IMProving Asthma Control Trial) including 1490 adults with chronic asthma, aged 15 72 years, with FEV1 50-90% of predicted and >= 12% increase in FEV1 after salbutamol administration, treated with either montelukast 10mg daily or salmeterol 50 mu g twice daily in addition to. fluticasone 200 mg, was undertaken. Asthma- related medical resource use included medical visits ( defined as either an unscheduled visit [to a general practitioner, a specialist or a nonmedical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids. Results A self-reported history of concomitant AR was identified in 60% of the patients (n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit ( odds ratio ( OR) 52.35, 95% confidence interval (CI) = 1.12 - 4.80) and asthma attack (OR = 1.35, 95% CI = 1.03 - 1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations. Conclusions Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR.
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- Lindstedt, Malin, et al.
(författare)
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Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response
- 2005
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 35:2, s. 199-206
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Tidskriftsartikel (refereegranskat)abstract
- Background: In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme-exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen-specific T cells. Objective: This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild-type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells. Methods: Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis. Results: Lipase-specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co-cultured with DCs pulsed with either hypoallergenic or wild-type lipase, as demonstrated by high IL-4 and IL-13, and low IFN-? production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non-responders. Conclusions: DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild-type lipase in vitro. Only allergen-pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase-specific T cells displayed a T-helper type 2 phenotype, which was not altered by hypoallergenic lipase-pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response. © 2005 Blackwell Publishing Ltd.
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- Oxelius, Vivi-Anne, et al.
(författare)
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Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies.
- 2006
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 36:12, s. 1616-1624
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Tidskriftsartikel (refereegranskat)abstract
- Background Several candidate genes have been found to be associated with the inflammatory response of IgE-mediated allergy, so also the immunoglobulin constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the IGHE gene on chromosome 14q32, 5'μ, δ, γ3, γ1, α1, γ2, γ4, e, α2, 3'. They are inherited in a Mendelian fashion and expressed randomly in allelic exclusion. The alternative and functionally different γ3, γ1 and γ2 gene variants are found in four IGHG haplotypes, coding four B cell variants. Objective The aim of this study was to assess the frequency of different IGHG genes in relation to phenotypes associated with allergy, in a case–control study. Methods We identified the constant heavy-chain genes of IgG in 198 allergic and non-allergic children participating in the Phase II of the International Study of Asthma and Allergy in Children. The IGHG genes were assessed by the alternative serum IgG subclass allotypes expressing the alternative alleles of γ3, γ1 and γ2 genes, using ELISA and double immunodiffusion. Results The IGHG*bfn haplotype (=B1 cells) and IGHG2*n allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells) was infrequent (16% vs. 52%, P<0.001) in allergic children with a family history of allergy, clinical manifest allergy and positive skin prick test (SPT). The frequency of IGHG genes was similar in children with maternal and paternal heredity and in children with wheezing, eczema or rhinitis, as well as in children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype was inversely related to allergy. Conclusions IgG allotypes, immunochemical and functional variants of IgG molecules from IGHG genes are associated with atopy. The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2 cells) with the IGHG2*-n allele is associated with low risk.
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- Persson, Carl, et al.
(författare)
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Roles of plasma exudation in asthma and COPD
- 2009
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 39:11, s. 1626-1629
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Cite this as: C. Persson and L. Uller, Clinical & Experimental Allergy, 2009 (39) 1626-1629.
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- Tufvesson, Ellen, et al.
(författare)
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Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness.
- 2007
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 37:7, s. 1067-1073
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Tidskriftsartikel (refereegranskat)abstract
- Background We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. Objective The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. Methods Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. Resutls Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6) pg/mu g total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20) and 0.20 (0.12-0.35) ng/mu g total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015 (0.011-0.021) compared with 0.010 (0.007-0.014) ng/mu g total protein]. The level of ECP remained elevated off season. Conclusions Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation.
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