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Diverging immune responses when allergy, type 1 diabetes and celiac disease coexist
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
Clinic of Paediatrics, Ryhov County Hospital, Jönköping, Sweden 4.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

An imbalance between different immune cells, among them T-cells and inflammatory cells, has been proposed to be part of the disease process in type 1 diabetes (T1D), celiac disease and allergy. T-cells and inflammatory cells exert their actions through cytokines and chemokines, and the secretion of those can be used to describe the cell milieu during an immune response.

This study included seventy-two children, diagnosed with T1D, celiac disease, allergy, or a combination of two of these diseases and compared to reference children. The study aimed to evaluate the secretion of 27 different cytokines and chemokines in cell culture supernatant after in vitro stimulation with disease-associated antigens (birch, gluten, insulin) detected by Luminex technique.

Combination of allergy with either T1D or celiac disease gave diverging results. Children with combination of T1D and allergy showed an increased secretion of several cytokines (IL-2, IL-4, IL-5, IL-7, IL-9, IL-10, IL-12, IL-15, IL-17 and CCL11), in comparison to almost all groups from birch stimulation. In contrast, when allergy was combined with celiac disease, the spontaneous secretion of IL-1β, IL-5, IL-6, IL-9, IL-10, IL-12 and CCL3 was decreased compared to children with T1D or allergy, as well as children with celiac disease alone, children with combination of T1D and allergy and reference children.

In conclusion, our results shed some light on the immune responses in children with common immunological diseases. Our study indicates diverging immune responses when allergy, type 1 diabetes and celiac disease coexist.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71911OAI: oai:DiVA.org:liu-71911DiVA: diva2:455270
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-09Bibliographically approved
In thesis
1. Combinations of type 1 diabetes, celiac disease and allergy: An immunological challenge
Open this publication in new window or tab >>Combinations of type 1 diabetes, celiac disease and allergy: An immunological challenge
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The immune system is composed of a complex network of different cell types protecting the body against various possible threats. Among these cells are T-helper (Th) cells type 1 (Th1) and type 2 (Th2), as well as T regulatory (Treg) cells. Th1 and Th2 are supposed to be in balance with each other, while Tregs regulate the immune response, by halting it when the desired effect, i.e. destroying the threat, is acquired. However, sometimes this intricate interplay in the immune system is disturbed, leading to diseases as type 1 diabetes (T1D), celiac disease or allergic disease. According to the paradigm claiming that Th1- and Th2-cells inhibit each other a coexistence of a Th1-deviated disease and a Th2-deviated disease seems unlikely.

This thesis aimed to examine the immune response with focus on subsets of T-cells in children with T1D, celiac disease, allergy, or a combination of two of these diseases, in comparison to reference children (healthy).

In line with previous findings we observed that children with celiac disease showed a decreased spontaneous Th2-associated secretion, whereas children with allergic disease showed increased birch- and cat-induced Th2-associated response.

The most remarkable results in this thesis are those observed in children with combinations of diseases. The combination of T1D and celiac disease decreased the Th1-associated response against several antigens, but instead displayed a more pronounced Treg-associated response. Further, in children with combined T1D and allergy an increased Th1- and Th2-associated response was seen to a general stimulus, and an increased birch-induced Th1-, Th2-, Treg- and pro-inflammatory response. In contrast, the combination of allergy and celiac disease showed a decreased spontaneous Th1-, Th2-, Treg- and pro-inflammatory response.

In conclusion, we observed that two Th1-deviated diseases in combination suppress the immune response and increase the regulatory activity. Further it seems that allergy has the ability to shift the immune response in diverging directions depending on which disease it is combined with. The observed suppressive effect might be due to exhaustion of the immune system from the massive pressure of two immunological diseases in combination, while the pronounced Treg response might be caused by an attempt to compensate for the dysfunction. These results shed some light on the intriguing and challenging network that constitutes the immune system, and hopefully give clues regarding disease prevention and treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 109 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1277
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71915 (URN)978-91-7393-021-5 (ISBN)
Public defence
2011-12-02, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
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Supervisors
Available from: 2011-11-09 Created: 2011-11-09 Last updated: 2011-11-17Bibliographically approved

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Kivling, AnnaNilsson, LennartFälth-Magnusson, KarinFaresjö, Maria

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