Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

M. Karoliina Hirvonen; Niina Lietzén; Robert Moulder; Santosh D. Bhosale; Jaakko Koskenniemi; Mari Vähä-Mäkilä; Mirja Nurmio; Matej Orešič; Jorma Ilonen; Jorma Toppari; Riitta Veijola; Heikki Hyöty; Harri Lähdesmäki; Mikael Knip; Lu Cheng; Riitta Lahesmaa

doi:10.1038/s41598-023-43039-4

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

M. Karoliina Hirvonen, Niina Lietzén, Robert Moulder, Santosh D. Bhosale, Jaakko Koskenniemi, Mari Vähä-Mäkilä, Mirja Nurmio, Matej Orešič, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Heikki Hyöty, Harri Lähdesmäki, Mikael Knip, Lu Cheng^*, Riitta Lahesmaa^*

^*Korresponderande författare för detta arbete

Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review

4 Citeringar (Scopus)

8 Nedladdningar (Pure)

Sammanfattning

Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.

Originalspråk	Engelska
Artikelnummer	15941
Antal sidor	11
Tidskrift	Scientific Reports
Volym	13
Nummer	1
DOI	https://doi.org/10.1038/s41598-023-43039-4
Status	Publicerad - 24 sep. 2023
MoE-publikationstyp	A1 Tidskriftsartikel-refererad

Finansiering

The authors are grateful to the DIPP families for their participation and the clinical personnel for excellent collaboration, working with the families and obtaining the samples and clinical data for the study. We also thank the staff of the DIPP Immunogenetics laboratory at University of Turku and the DIPP autoantibody laboratory at University of Oulu. The mass spectrometry analyses presented in this work were performed at the Proteomics Core Facility of the Turku Bioscience Centre that belongs to Biocenter Finland infrastructure network. We thank Pekka Haapaniemi (Proteomics Facility, Turku Bioscience Centre, Finland) for his invaluable help in sample preparation, and also other facility members for the excellent technical support. L. C. and H. L. acknowledges the computational resources provided by the Aalto Science-IT project and CSC—IT Center for Science, Finland. Figure was created with Biorender.com. The authors are grateful to the DIPP families for their participation and the clinical personnel for excellent collaboration, working with the families and obtaining the samples and clinical data for the study. We also thank the staff of the DIPP Immunogenetics laboratory at University of Turku and the DIPP autoantibody laboratory at University of Oulu. The mass spectrometry analyses presented in this work were performed at the Proteomics Core Facility of the Turku Bioscience Centre that belongs to Biocenter Finland infrastructure network. We thank Pekka Haapaniemi (Proteomics Facility, Turku Bioscience Centre, Finland) for his invaluable help in sample preparation, and also other facility members for the excellent technical support. L. C. and H. L. acknowledges the computational resources provided by the Aalto Science-IT project and CSC—IT Center for Science, Finland. Figure 1 was created with Biorender.com.

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10.1038/s41598-023-43039-4

s41598-023-43039-4Slutlig publicerad version, 1,94 MBLicens: CC BY

https://urn.fi/URN:NBN:fi-fe202402096358

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Hirvonen, M. K., Lietzén, N., Moulder, R., Bhosale, S. D., Koskenniemi, J., Vähä-Mäkilä, M., Nurmio, M., Orešič, M., Ilonen, J., Toppari, J., Veijola, R., Hyöty, H., Lähdesmäki, H., Knip, M., Cheng, L., & Lahesmaa, R. (2023). Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes. Scientific Reports, 13(1), Artikel 15941. https://doi.org/10.1038/s41598-023-43039-4

@article{3945d7051912418d9204c0d9220c0e18,

title = "Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes",

abstract = "Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.",

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Hirvonen, MK, Lietzén, N, Moulder, R, Bhosale, SD, Koskenniemi, J, Vähä-Mäkilä, M, Nurmio, M, Orešič, M, Ilonen, J, Toppari, J, Veijola, R, Hyöty, H, Lähdesmäki, H, Knip, M, Cheng, L & Lahesmaa, R 2023, 'Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes', Scientific Reports, vol. 13, nr. 1, 15941. https://doi.org/10.1038/s41598-023-43039-4

TY - JOUR

T1 - Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

AU - Hirvonen, M. Karoliina

AU - Lietzén, Niina

AU - Moulder, Robert

AU - Bhosale, Santosh D.

AU - Koskenniemi, Jaakko

AU - Vähä-Mäkilä, Mari

AU - Nurmio, Mirja

AU - Orešič, Matej

AU - Ilonen, Jorma

AU - Toppari, Jorma

AU - Veijola, Riitta

AU - Hyöty, Heikki

AU - Lähdesmäki, Harri

AU - Knip, Mikael

AU - Cheng, Lu

AU - Lahesmaa, Riitta

PY - 2023/9/24

Y1 - 2023/9/24

N2 - Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.

AB - Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.

UR - https://www.scopus.com/pages/publications/85171842365

U2 - 10.1038/s41598-023-43039-4

DO - 10.1038/s41598-023-43039-4

M3 - Article

C2 - 37743383

AN - SCOPUS:85171842365

SN - 2045-2322

VL - 13

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 15941

ER -

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

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