Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies

Inna Starskaia, Milla Valta, Sami Pietilä, Tomi Suomi, Sirpa Pahkuri, Ubaid Ullah Kalim, Omid Rasool, Emilie Rydgren, Heikki Hyöty, Mikael Knip, Riitta Veijola, Jorma Ilonen, Jorma Toppari, Johanna Lempainen (), Laura L. Elo () and Riitta Lahesmaa ()
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Inna Starskaia: University of Turku and Åbo Akademi University
Milla Valta: University of Turku
Sami Pietilä: University of Turku and Åbo Akademi University
Tomi Suomi: University of Turku and Åbo Akademi University
Sirpa Pahkuri: University of Turku
Ubaid Ullah Kalim: University of Turku and Åbo Akademi University
Omid Rasool: University of Turku and Åbo Akademi University
Emilie Rydgren: University of Turku and Åbo Akademi University
Heikki Hyöty: and Fimlab Laboratories
Mikael Knip: University of Helsinki
Riitta Veijola: Oulu University Hospital and University of Oulu
Jorma Ilonen: University of Turku
Jorma Toppari: University of Turku
Johanna Lempainen: University of Turku
Laura L. Elo: University of Turku and Åbo Akademi University
Riitta Lahesmaa: University of Turku and Åbo Akademi University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Previous studies have revealed heterogeneity in the progression to clinical type 1 diabetes in children who develop islet-specific antibodies either to insulin (IAA) or glutamic acid decarboxylase (GADA) as the first autoantibodies. Here, we test the hypothesis that children who later develop clinical disease have different early immune responses, depending on the type of the first autoantibody to appear (GADA-first or IAA-first). We use mass cytometry for deep immune profiling of peripheral blood mononuclear cell samples longitudinally collected from children who later progressed to clinical disease (IAA-first, GADA-first, ≥2 autoantibodies first groups) and matched for age, sex, and HLA controls who did not, as part of the Type 1 Diabetes Prediction and Prevention study. We identify differences in immune cell composition of children who later develop disease depending on the type of autoantibodies that appear first. Notably, we observe an increase in CD161 expression in natural killer cells of children with ≥2 autoantibodies and validate this in an independent cohort. The results highlight the importance of endotype-specific analyses and are likely to contribute to our understanding of pathogenic mechanisms underlying type 1 diabetes development.

Date: 2024
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DOI: 10.1038/s41467-024-47918-w

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