ESPE Abstracts (2015) 84 P-1-31


Type 1 Diabetes Onset: A Story of Innate and Adaptive Immune Cells?

Ana Laura Fitasa, Catarina Martinsb, Anabela Alonsoa, Glória Nunesb, Rosa Pinaa, Daniela Amarala, Sigurd Lenzenc, Lurdes Lopesa, Luis Miguel Borregob & Catarina Limberta,b


aHospital D. Estefânia, CHLC, Lisbon, Portugal; bCEDOC – NOVA Medical School/FCM – UNL, Lisbon, Portugal; cHannover Medical School, Institute of Clinical Biochemistry, Hannover, Germany

Background: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease. A more complex immunological picture is being unraveled, with a key role of innate immune cells at disease onset and maintenance. For new therapies based on immune-modulation to be possible, immune characterization of T1D patients is crucial.

Objective and hypotheses: We aimed to characterise innate and adaptive immune cells of T1D children at a well-defined ‘onset-window’ of disease, and to correlate with the metabolic status of patients at this stage.

Method: Blood samples from 41 T1D children, followed at a Paediatric Central Hospital, were evaluated by flow cytometry, <14d after diagnosis and were matched to controls. HbA1c was also evaluated by HPLC at the same time point in T1D. Statistical significance was defined by a P-value of <0.05.

Results: At disease onset, T1D children presented significantly higher T and B cell percentages and lower NK cells compared to controls. Within T cells, T1D children exhibited significantly decreased Th17 and Tc17 cells. Regarding leukocytes, monocytes were significantly impaired in T1D children. However, neutrophils and IL17-producing cells correlated inversely with HbA1c. Separating T1D patients in high- and low-HbA1c (≥12%vs<12%), high-HbA1c patients showed significantly reduced neutrophils, Th17 and Tc17 cells, compared to low-HbA1c and controls.

Conclusion: T1D onset presented lower circulating innate cells (NK cells, monocytes) and IL17-producing cells, which may reflect increased migration of these cells to pancreatic tissue at this stage, associated with tissue damage. Longer pre-clinical hyperglycemic patients presented even less circulating IL17-producing cells, and also less neutrophils, which can be due to the capacity of Th17 to attract neutrophils to the site of inflammation. These results suggest that metabolic status influences the migration pattern of immune cells. Our data point toward a relevant role of neutrophils and IL17-producing cells as future targets for immune response modulation.

Funding: This work was supported by Sanofi.

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