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Immune Cell and Cytokine Patterns in Children with Type 1 Diabetes Mellitus Undergoing a Remission Phase: A Longitudinal Study

2018Journal article Open access
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dc.contributor.authorFitas, AL
dc.contributor.authorMartins, C
dc.contributor.authorBorrego, LM
dc.contributor.authorLopes, L
dc.contributor.authorJörns, A
dc.contributor.authorLenzen, S
dc.contributor.authorLimbert, C
dc.date.accessioned2021-05-27T06:35:26Z
dc.date.available2021-05-27T06:35:26Z
dc.date.issued2018
dc.description.abstractObjective: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPediatr Diabetes . 2018 Aug;19(5):963-971pt_PT
dc.identifier.doi10.1111/pedi.12671pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3697
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectAdolescentpt_PT
dc.subjectC-Peptidept_PT
dc.subjectCase-Control Studiespt_PT
dc.subjectChildpt_PT
dc.subjectCytokinespt_PT
dc.subjectDiabetes Mellitus, Type 1pt_PT
dc.subjectDisease Progressionpt_PT
dc.subjectFemalept_PT
dc.subjectHumanspt_PT
dc.subjectLeukocyte Countpt_PT
dc.subjectLongitudinal Studiespt_PT
dc.subjectMalept_PT
dc.subjectHDE END PEDpt_PT
dc.titleImmune Cell and Cytokine Patterns in Children with Type 1 Diabetes Mellitus Undergoing a Remission Phase: A Longitudinal Studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage971pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage963pt_PT
oaire.citation.titlePediatric diabetespt_PT
oaire.citation.volume19pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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