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The ABBOS-peptide from bovine serum albumin causes an IFN-γ and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2000 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 47, no 3, 199-207 p.Article in journal (Refereed) Published
Abstract [en]

The ABBOS-peptide from bovine serum albumin (BSA) in cow’s milk has been suggested to initiate the autoimmune process against the β-cells leading to type 1 diabetes. The aim of this study was to elucidate if the ABBOS-peptide is a possible trigger of type 1 diabetes. The cytokines IL-4 and IFN-γ were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. Sixteen children with newly diagnosed type 1 diabetes were compared with 10 healthy controls matched for the diabetes associated HLA-type DR3/4. Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. Increased mRNA expression for IFN-γ and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. Low expression of IFN-γ mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. Expression of IFN-γ and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. ABBOS may have a role as a reactive epitope in the upregulation of the autoimmune process against the β-cells but ABBOS does not seem to cause any specific Th1 response. An increased mRNA expression could also be seen in lymphocytes from healthy controls. Thus, the ABBOS-peptide might just cause or reflect an unspecific immune activity.

Place, publisher, year, edition, pages
2000. Vol. 47, no 3, 199-207 p.
Keyword [en]
ABBOS, IFN-γ, IL-4, Type 1 diabetes, Th-lymphocytes
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25986DOI: 10.1016/S0168-8227(99)00127-8Local ID: 10438OAI: oai:DiVA.org:liu-25986DiVA: diva2:246534
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The Importance of Cell-Mediated Immunity for the Development of Type 1 Diabetes
Open this publication in new window or tab >>The Importance of Cell-Mediated Immunity for the Development of Type 1 Diabetes
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Type I (insulin-dependent) diabetes mellitus is an autoimmune disease characterised by infiltration of T-lymphocytes in the islets of Langerhans. In particular, activated Th1-like lymphocytes secreting IFN-γ are suggested to contribute to the inflammatory process and the destruction of ß-cells, whereas Th2-like cells producing IL-4 might even be protective. Environmental factors (diet, viruses, stress etc.) and autoantigens, e.g. Glutamic Acid Decarboxylase (GAD65) and insulin, are suggested to initiate the autoimmune process resulting in type I diabetes.

Aim To estimate the immunological balance of Th1/Th2-like lymphocytes, spontaneously and after stimulation with antigens, in high-risk first degree relatives of type 1 diabetic children and in children with newly diagnosed type 1 diabetes.

Materials and methods Peripheral blood mononuclear cells (PBMC) from healthy high-risk first-degree relatives (ICA ≥ 20) and newly diagnosed type 1 diabetic children were examined and compared with the response seen in PBMC from healthy controls matched for age and HLA-type (DR3 and/or DR4).

Expression of IFN-γ and IL-4 mRNA was determined by RT-PCR or real-time RTPCR and IFN-γ and IL-4 by ELISPOT or ELISA, spontaneously and after stimulation with GAD65 , insulin, bovine serum albumin (BSA), the ABBOS-peptide and ß-lactoglobulin (ßLG). Cytokine expression and secretion was compared to the production of diabetes-associated autoantibodies and to the secretion of endogenous insulin.

Results The epitope of GAD65, that mimics the Coxsackie B virus, caused increased IFN-γ mRNA expression in activated Th1-like lymphocytes from newly diagnosed diabetic children. This suggests that GAD65 might be involved in the development of type I diabetes. On the contrary, cow's milk proteins caused increased IFN-γ and IL- 4 mRNA expression in activated Th1- and Th2-like lymphocytes from both diabetic and healthy children. This does not support the hypothesis that cow's milk antigens are important for the development of type 1 diabetes.

Overwhelming secretion of IFN-γ was observed in high-risk first-degree relatives of type 1 diabetic children. High-risk individuals still have the ability to change a Th1-like immune deviation into a more protective Th2-like response in the presence of GAD65 and insulin.

Conclusions GAD65, but not cow's milk proteins, causes a Th1-like deviation in type 1 diabetic children. High-risk individuals are capable to deviate a Th1-like immune system into a more protective Th2-like response in the presence of autoantigens. These results can be useful in future therapeutic approaches.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 130 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 644
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28590 (URN)13744 (Local ID)91-7219-745-5 (ISBN)13744 (Archive number)13744 (OAI)
Public defence
2000-10-20, Berzeliussalen, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-08-14Bibliographically approved

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Karlsson, Maria G. E.Ludvigsson, Johnny

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