The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development

Abstract

Type 1 Diabetes (T1D) is considered to be a T-helper- (Th-) 1 autoimmune disease; however, T1D pathogenesis likely involves many factors, and sufficient tools for autoreactive T cell detection for the study of this disease are currently lacking. In this study, using gene expression microarrays, we analysed the effect of diabetes-associated autoantigens on peripheral blood mononuclear cells (PBMCs) with the purpose of identifying (pre)diabetes-associated cell processes. Twelve patients with recent onset T1D, 18 first-degree relatives of the TD1 patients (DRL; 9/18 autoantibody positive), and 13 healthy controls (DV) were tested. PBMCs from these individuals were stimulated with a cocktail of diabetes-associated autoantigens (proinsulin, IA-2, and GAD65-derived peptides). After 72 hours, gene expression was evaluated by high-density gene microarray. The greatest number of functional differences was observed between relatives and controls (69 pathways), from which 15% of the pathways belonged to “immune response-related” processes. In the T1D versus controls comparison, more pathways (24%) were classified as “immune response-related.” Important pathways that were identified using data from the T1D versus controls comparison were pathways involving antigen presentation by MHCII, the activation of Th17 and Th22 responses, and cytoskeleton rearrangement-related processes. Genes involved in Th17 and TGF-beta cascades may represent novel, promising (pre)diabetes biomarkers.

Not Only Glycaemic But Also Other Metabolic Factors Affect T Regulatory Cell Counts and Proinflammatory Cytokine Levels in Women with Type 1 Diabetes

“…Such imbalances could be very important because the equilibrium between these two molecules determines CD4 T cell fate and the type of subsequently generated immune responses. The suspicion that the Treg/Th17 balance is very important for the development of T1D is also supported by our previously published study [ 23 ]. Moreover, it has been previously proposed that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from beta cell autoantibody positivity to clinically apparent type 1 diabetes [ 24 ].…”

Some Haematological Parameters in Patients with Type-1 Diabetes in Sokoto, North Western Nigeria

“…Type2 diabetes on the other hand is characterized by resistance to insulin action and suboptimal insulin secretory response. Causes of diabetes ranges from autoimmunemediated destruction of beta cells and idiopathic destruction or failure of beta cells [2,3]. About 5-10% of the total cases of diabetes worldwide are due to T1D.…”

Targeting Inflammation by Flavonoids: Novel Therapeutic Strategy for Metabolic Disorders

“…Stress triggers the production of auto-antigens such as insulin, tyrosine phosphatase, glutamic acid decarboxylase, and islet cell antigen 69 from β cells [94,95]. These auto-antigens are recognized by the auto-antibodies and auto-reactive T cells that provide specificity to autoimmune destruction [96,97]. The infiltration of macrophages, dendritic cells, and CD4 + and CD8 + T cells, as well as the balance of CD4 + Th1/Th2, is responsible for the damage of β cells.…”