Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: a longitudinal study

Ana Laura Fitas, Catarina Martins, Luís Miguel Borrego, Lurdes Lopes, Anne Jörns, Sigurd Lenzen, Catarina Limbert

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: Type 1 diabetes (T1D) develops in distinct stages, before and after disease onset. Whether the natural course translates into different immunologic patterns is still uncertain. This study aimed at identifying peripheral immune patterns at key time-points, in T1D children undergoing remission phase.

METHODS: Children with new-onset T1D and healthy age and gender-matched controls were recruited at a paediatric hospital. Peripheral blood samples were evaluated by flow cytometry at three longitudinal time-points: onset (T1), remission phase (T2) and established disease (T3). Cytokine levels were quantified by multiplex assay. Fasting C-peptide, HbA1c and 25OHD were also measured.

RESULTS: T1D children (n=28; 10.0±2.6 years) showed significant differences from controls in circulating neutrophils, T helper (Th)17 and natural killer (NK) cells, with relevant variations during disease progression. At onset, neutrophils, NK, Th17 and T cytotoxic (Tc)17 cells were decreased. As disease progressed, neutrophil counts recovered whereas NK counts remained low. Th17 and Tc17 cells behaviour followed the neutrophil variation pattern. B-cells were lowest in the remission phase and regulatory T-cells significantly declined after remission. Two cytokine response profiles were identified. Low cytokine-responders showed higher circulating fasting C-peptide levels at onset and longer remission periods. C-peptide inversely correlated with pro-inflammatory and cytotoxic cells.

CONCLUSIONS/INTERPRETATION: Our data suggest an association between immune cells, cytokine patterns and metabolic counterparts. The dynamic changes of circulating immune cells during disease progression involve key innate and acquired immune cell types. This longitudinal picture of T1D progression may enable disease staging and patient stratification, essential for individualized treatment.

Original languageEnglish
Pages (from-to)963-971
Number of pages9
JournalPediatric diabetes
Volume19
Issue number5
Early online date12 Mar 2018
DOIs
Publication statusPublished - Aug 2018

Keywords

  • C-Peptide
  • Cytokines
  • Diabetes Mellitus
  • Lymphocytes
  • Neutrophils
  • Type 1

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