Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies
Starskaia, Inna; Valta, Milla; Pietilä, Sami; Suomi, Tomi; Pahkuri, Sirpa; Kalim, Ubaid Ullah; Rasool, Omid; Rydgren, Emilie; Hyöty, Heikki; Knip, Mikael; Veijola, Riitta; Ilonen, Jorma; Toppari, Jorma; Lempainen, Johanna; Elo, Laura L.; Lahesmaa, Riitta (2024)
Starskaia, Inna
Valta, Milla
Pietilä, Sami
Suomi, Tomi
Pahkuri, Sirpa
Kalim, Ubaid Ullah
Rasool, Omid
Rydgren, Emilie
Hyöty, Heikki
Knip, Mikael
Veijola, Riitta
Ilonen, Jorma
Toppari, Jorma
Lempainen, Johanna
Elo, Laura L.
Lahesmaa, Riitta
2024
3810
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202407087544
https://urn.fi/URN:NBN:fi:tuni-202407087544
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [19288]