Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age

Tutkimustuotos: Lehtiartikkelivertaisarvioitu

Standard

Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age. / Kallionpää, Henna; Somani, Juhi; Tuomela, Soile; Ullah, Ubaid; De Albuquerque, Rafael; Lönnberg, Tapio; Komsi, Elina; Siljander, Heli; Honkanen, Jarno; Härkönen, Taina; Peet, Aleksandr; Tillmann, Vallo; Chandra, Vikash; Anagandula, Mahesh Kumar; Frisk, Gun; Otonkoski, Timo; Rasool, Omid; Lund, Riikka; Lähdesmäki, Harri; Knip, Mikael; Lahesmaa, Riitta.

julkaisussa: DIABETES, Vuosikerta 68, Nro 10, 01.10.2019, s. 2024-2034.

Tutkimustuotos: Lehtiartikkelivertaisarvioitu

Harvard

Kallionpää, H, Somani, J, Tuomela, S, Ullah, U, De Albuquerque, R, Lönnberg, T, Komsi, E, Siljander, H, Honkanen, J, Härkönen, T, Peet, A, Tillmann, V, Chandra, V, Anagandula, MK, Frisk, G, Otonkoski, T, Rasool, O, Lund, R, Lähdesmäki, H, Knip, M & Lahesmaa, R 2019, 'Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age', DIABETES, Vuosikerta. 68, Nro 10, Sivut 2024-2034. https://doi.org/10.2337/db19-0287

APA

Kallionpää, H., Somani, J., Tuomela, S., Ullah, U., De Albuquerque, R., Lönnberg, T., ... Lahesmaa, R. (2019). Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age. DIABETES, 68(10), 2024-2034. https://doi.org/10.2337/db19-0287

Vancouver

Kallionpää H, Somani J, Tuomela S, Ullah U, De Albuquerque R, Lönnberg T et al. Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age. DIABETES. 2019 loka 1;68(10):2024-2034. https://doi.org/10.2337/db19-0287

Author

Kallionpää, Henna ; Somani, Juhi ; Tuomela, Soile ; Ullah, Ubaid ; De Albuquerque, Rafael ; Lönnberg, Tapio ; Komsi, Elina ; Siljander, Heli ; Honkanen, Jarno ; Härkönen, Taina ; Peet, Aleksandr ; Tillmann, Vallo ; Chandra, Vikash ; Anagandula, Mahesh Kumar ; Frisk, Gun ; Otonkoski, Timo ; Rasool, Omid ; Lund, Riikka ; Lähdesmäki, Harri ; Knip, Mikael ; Lahesmaa, Riitta. / Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age. Julkaisussa: DIABETES. 2019 ; Vuosikerta 68, Nro 10. Sivut 2024-2034.

Bibtex - Lataa

@article{469b16b33d2943c0b5651c1d99b5bef8,
title = "Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age",
abstract = "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 β-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 β-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 β-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.",
author = "Henna Kallionp{\"a}{\"a} and Juhi Somani and Soile Tuomela and Ubaid Ullah and {De Albuquerque}, Rafael and Tapio L{\"o}nnberg and Elina Komsi and Heli Siljander and Jarno Honkanen and Taina H{\"a}rk{\"o}nen and Aleksandr Peet and Vallo Tillmann and Vikash Chandra and Anagandula, {Mahesh Kumar} and Gun Frisk and Timo Otonkoski and Omid Rasool and Riikka Lund and Harri L{\"a}hdesm{\"a}ki and Mikael Knip and Riitta Lahesmaa",
year = "2019",
month = "10",
day = "1",
doi = "10.2337/db19-0287",
language = "English",
volume = "68",
pages = "2024--2034",
journal = "DIABETES",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "10",

}

RIS - Lataa

TY - JOUR

T1 - Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age

AU - Kallionpää, Henna

AU - Somani, Juhi

AU - Tuomela, Soile

AU - Ullah, Ubaid

AU - De Albuquerque, Rafael

AU - Lönnberg, Tapio

AU - Komsi, Elina

AU - Siljander, Heli

AU - Honkanen, Jarno

AU - Härkönen, Taina

AU - Peet, Aleksandr

AU - Tillmann, Vallo

AU - Chandra, Vikash

AU - Anagandula, Mahesh Kumar

AU - Frisk, Gun

AU - Otonkoski, Timo

AU - Rasool, Omid

AU - Lund, Riikka

AU - Lähdesmäki, Harri

AU - Knip, Mikael

AU - Lahesmaa, Riitta

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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 β-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 β-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 β-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.

AB - 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 β-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 β-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 β-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.

UR - http://www.scopus.com/inward/record.url?scp=85070382391&partnerID=8YFLogxK

U2 - 10.2337/db19-0287

DO - 10.2337/db19-0287

M3 - Article

C2 - 31311800

AN - SCOPUS:85070382391

VL - 68

SP - 2024

EP - 2034

JO - DIABETES

JF - DIABETES

SN - 0012-1797

IS - 10

ER -

ID: 37377955