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Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
Thermo Fisher Sci, Uppsala, Sweden.
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2018 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 9, p. 1186-1194Article in journal (Refereed) Published
Abstract [en]

Background: Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied.

Objective: To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals.

Methods: Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders.

Results: The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with B-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51).

Conclusions: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics.

Clinical relevance: We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.

Place, publisher, year, edition, pages
2018. Vol. 48, no 9, p. 1186-1194
Keywords [en]
asthma, clinical immunology, eosinophils, IgE, immunologic tests
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-364158DOI: 10.1111/cea.13135ISI: 000443113000010PubMedID: 29575179OAI: oai:DiVA.org:uu-364158DiVA, id: diva2:1260146
Funder
Swedish Foundation for Strategic Research VINNOVASwedish Heart Lung FoundationSwedish Asthma and Allergy AssociationAvailable from: 2018-11-01 Created: 2018-11-01 Last updated: 2018-11-26Bibliographically approved
In thesis
1. Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics
Open this publication in new window or tab >>Study of biomarkers for improved diagnosis and therapy monitoring in young asthmatics
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Type-2 asthma is often related to atopy and is characterized by elevated type-2 biomarkers. However, less is known about the pathophysiology of non-type 2 asthma, factors associated therewith, and the stability of different asthma phenotypes over time.

Aims: To identify an IgE antibody concentration and putative biomarkers that better separate non-type 2 from type-2 asthma. To study the association between longitudinal changes in inflammatory biomarkers and clinical outcomes. To investigate the pattern of IgE sensitization to different cat allergen components and its impact on type-2 biomarkers in young asthmatics.

Methods: The present thesis is based on the MIDAS asthma cohort, which includes asthmatics (n = 408) and healthy controls (n = 118), aged 10–35 years at baseline, with a follow-up visit 43{23-65} months later. All the subjects were characterized with regard to IgE sensitization, inflammation was assessed based on fractional exhaled NO (FeNO), blood eosinophil count (B-Eos) and other biomarkers, both type-2 and non-type 2, and lung function was evaluated with spirometry.

Results: FeNO and B-Eos maintained associations with clinical asthma outcomes in the IgE antibody concentration range 0.10–0.34 kUA/L, but not below 0.10 kUA/L. Non-atopic asthmatics with perceived cow’s milk hypersensitivity had poorer asthma-related quality of life than those with atopic asthma, and were characterized by clinically significant non-type 2 inflammation. Furthermore, longitudinal increase in height-adjusted FeNO associated independently with decline in lung function. IgE sensitization to cat lipocalins and/or cat serum albumin were independently associated with FeNO and B-Eos.

Conclusions: Our findings demonstrated that a cut-off of 0.10 kUA/L for IgE antibodies appeared to be useful for ruling out type-2 asthma in young subjects. A subgroup of non-atopic asthmatics was characterized by perceived cow’s milk hypersensitivity and non-type 2 inflammation. Longitudinal changes in FeNO associated with lung function decline in asthmatics. IgE sensitization to minor cat allergen components may promote both local and systemic type 2 inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1519
Keywords
Asthma phenotypes, IgE sensitization, atopy, cat allergen components, exhaled NO, airway hyper-responsiveness, lung function, asthma-related quality of life.
National Category
Respiratory Medicine and Allergy Pediatrics
Identifiers
urn:nbn:se:uu:diva-366892 (URN)978-91-513-0517-2 (ISBN)
Public defence
2019-01-29, Sal 42, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:15 (Swedish)
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Supervisors
Available from: 2018-12-28 Created: 2018-11-26 Last updated: 2019-02-01

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Tsolakis, NikolaosMalinovschi, AndreiNordvall, LennartJanson, ChristerBorres, Magnus PAlving, Kjell

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Paediatric Inflammation ResearchClinical PhysiologyDepartment of Women's and Children's HealthLung- allergy- and sleep research
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