uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Early Detection of Peripheral Blood Cell Signature in Children Developing beta-Cell Autoimmunity at a Young Age
Univ Turku, Turku Biosci Ctr, Turku, Finland; Åbo Akad Univ, Turku, Finland.
Aalto Univ, Dept Comp Sci, Sch Sci, Espoo, Finland.
Univ Turku, Turku Biosci Ctr, Turku, Finland; Åbo Akad Univ, Turku, Finland.
Univ Turku, Turku Biosci Ctr, Turku, Finland; Åbo Akad Univ, Turku, Finland.
Show others and affiliations
2019 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, no 10, p. 2024-2034Article in journal (Refereed) Published
Abstract [en]

The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive beta-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4(+) and CD8(+) T cells as well as CD4(-)CD8(-) cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed beta-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that high IL32 in case samples was contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and beta-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.

Place, publisher, year, edition, pages
2019. Vol. 68, no 10, p. 2024-2034
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-395419DOI: 10.2337/db19-0287ISI: 000487068200014PubMedID: 31311800OAI: oai:DiVA.org:uu-395419DiVA, id: diva2:1363022
Funder
EU, Horizon 2020Novo Nordisk, 115797EU, FP7, Seventh Framework Programme, 202063Available from: 2019-10-22 Created: 2019-10-22 Last updated: 2019-10-22Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Anagandula, Mahesh KumarFrisk, Gun

Search in DiVA

By author/editor
Anagandula, Mahesh KumarFrisk, GunLund, Riikka
By organisation
Clinical Immunology
In the same journal
Diabetes
Endocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 2 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf