Nugnes, Rosa (2013) Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression. [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression.
Autori:
AutoreEmail
Nugnes, Rosarosanugnes@gmail.com
Data: 1 Aprile 2013
Numero di pagine: 88
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Oncologia ed endocrinologia molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
nomeemail
Santoro, Massimomasantor@unina.it
Tutor:
nomeemail
Matarese, Giuseppegiuseppe.matarese@cnr.it
Data: 1 Aprile 2013
Numero di pagine: 88
Parole chiave: type 1 diabetes, biomarkers
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/13 - Endocrinologia
Depositato il: 11 Apr 2013 14:05
Ultima modifica: 22 Lug 2014 13:04
URI: http://www.fedoa.unina.it/id/eprint/9324
DOI: 10.6092/UNINA/FEDOA/9324

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-secreting pancreatic β-cells in genetically susceptible individuals, whose incidence is increasing worldwide. So far, our ability to curb this pathogenic immune response is limited by the poor understanding of the exact nature and kinetics of the immunological mechanisms leading to T1D. Indeed, triggers of islet autoimmunity and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. Several scientific evidence supports a crucial role for the environment, which is also suggested by the rapid increase of incidence of this autoimmune disease. The search for a single cause of T1D has been vain, more probably there are a number of different factors that may contribute either to the initiating of the disease process or precipitating the manifest disease in subjects on their way to get diabetes. High living standard, good parent education, few siblings, pronounced hygiene, are all factors with possible important effects on immune system and autoimmune risk. In addition, the recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of T1D, as a precipitating factor. Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression. We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in type 1 diabetes patients at onset, at 12 and at 24 months after diagnosis, in high-risk subjects and in non-diabetic controls. A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs. The meta-immunological profile changed significantly among the three studied groups and in patients over time, and a specific signature that associated with worsening disease was identified. Finally, markers to predict residual β-cell function up to one year after diagnosis were identified in a multivariate logistic regression model. This latter model, measuring age, body mass index (BMI), fasting C-peptide (C-pep), number of circulating CD3+CD16+CD56+ cells and percentage of CD1c+CD19-CD14-CD303- type 1 myeloid dendritic cells (mDC1s) at disease onset had a significant predictive value. The identification of a specific meta-immunological profile associated to disease status may contribute to understand the basis of diabetes and its progression, and provide novel biomarkers that could help clinicians in disease monitoring and in the choose of the most appropriate therapeutic approach according to disease status and aggressiveness.

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