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Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study
Author(s) -
Fitas Ana Laura,
Martins Catarina,
Borrego Luís Miguel,
Lopes Lurdes,
Jörns Anne,
Lenzen Sigurd,
Limbert Catarina
Publication year - 2018
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12671
Subject(s) - medicine , immune system , cytokine , immunology , cytotoxic t cell , flow cytometry , biology , biochemistry , in vitro
Objective 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 pediatric hospital. Peripheral blood samples were evaluated by flow cytometry at 3 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 behavior 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 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.