Biomarkers in type 1 diabetes

Tooley, James E.; Herold, Kevan C.

doi:10.1097/med.0000000000000076

Cited by 15 publications

(6 citation statements)

References 53 publications

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“…Autoantibodies to these molecules are both diagnostic and prognostic of disease development; however, routine use of autoantibody levels as a diagnostic tool is cumbersome, at best. Prevention trials to stop or slow the natural progression of T1D could be designed and executed better if we had available robust biomarkers of the processes that ultimately are at the origin of the disease [ 6 – 7 ]. Due to the limitations of current biomarkers, there is an unmet clinical need to identify novel T1D biomarkers to improve the sensitivity and specificity of T1D prediction and disease monitoring after treatment.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes

et al. 2015

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Type 1 diabetes (T1D) and type 2 diabetes (T2D) are associated with functional beta cell loss due to ongoing inflammation. Despite shared similarities, T1D is an autoimmune disease with evidence of autoantibody production, as well as a role for exocrine pancreas involvement. Our hypothesis is that differential protein expression occurs in disease stratified pancreas tissues and regulated proteins from endocrine and exocrine tissues are potential markers of disease and potential therapeutic targets. The study objective was to identify novel proteins that distinguish the pancreas from donors with T1D from the pancreas from patients with T2D, or autoantibody positive non-diabetic donors. Detailed quantitative comprehensive proteomic analysis was applied to snap frozen human pancreatic tissue lysates from organ donors without diabetes, with T1D-associated autoantibodies in the absence of diabetes, with T1D, or with T2D. These disease-stratified human pancreas tissues contain exocrine and endocrine tissues (with dysfunctional islets) in the same microenvironment. The expression profiles of several of the proteins were further verified by western blot. We identified protein panels that are significantly and uniquely upregulated in the three disease-stratified pancreas tissues compared to non-disease control tissues. These proteins are involved in inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to, and likely involved in, T1 and T2 diabetes pathogenesis. Several new proteins were differentially upregulated in prediabetic, T1D, and T2D pancreas. The results identify proteins that could serve as novel prognostic, diagnostic, and therapeutic tools to preserve functional islet mass in Type 1 Diabetes.

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Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes

et al. 2015

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“…In the clinic, it is common to test for the existence of diabetes-associated autoantibodies, including GAD65, IAA, IA2, IGRP, and ZnT8 for diagnosis of patients with T1D ( 83 , 84 ). It has been discussed that the titer and number of autoantibodies are a useful biomarker to predict disease progress in patients with T1D ( 84 , 85 ). Currently, assays for measuring antigen-specific CD8 or CD4 T cells in both freshly isolated and cryopreserved peripheral blood mononuclear cells samples with flow cytometry-based HLA multimers are in progress and have been validated ( 84 ).…”

Section: To Move the Field Forward: Reliable And Robust Immune Biomarmentioning

confidence: 99%

Antigen-Specific Regulatory T Cells and Low Dose of IL-2 in Treatment of Type 1 Diabetes

2016

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Regulatory T cells (Tregs) play an important role in preventing effector T-cell (Teff) targeting of self-antigens that can lead to tissue destruction in autoimmune settings, including type 1 diabetes (T1D). Autoimmunity is caused in part by an imbalance between Teff and Tregs. Early attempts to treat with immunosuppressive agents have led to serious side effects, thus requiring a more targeted approach. Low-dose IL-2 (LD IL-2) can provide immunoregulation with few side effects by preferentially acting on Tregs to drive tolerance. The concept of LD IL-2 as a therapeutic approach is supported by data in mouse models where autoimmunity is cured and further strengthened by success in human clinical studies in hepatitis C virus-induced vasculitis, chronic graft-versus-host disease, and Alopecia areata. Treatment will require identification of a safe therapeutic window, which is a difficult task given that patients are reported to have deficient or defective IL-2 production or signaling and have experienced mild activation of NK cells and eosinophils with LD IL-2 therapy. In T1D, an LD IL-2 clinical trial concluded that Tregs can be safely expanded in humans; however, the study was not designed to address efficacy. Antigen-specific therapies have also aimed at regulation of the autoimmune response but have been filled with disappointment despite an extensive list of diverse islet antigens tested in humans. This approach could be enhanced through the addition of LD IL-2 to the antigenic treatment regimen to improve the frequency and function of antigen-specific Tregs, without global immunosuppression. Here, we will discuss the use of LD IL-2 and islet antigen to enhance antigen-specific Tregs in T1D and focus on what is known about their immunological impact, their safety, and potential efficacy, and need for better methods to identify therapeutic effectiveness.

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“…So far, several T-cell assays identify diabetes-specific CD4+ and CD8+ T cells (e.g. cellular immunoblotting, ELISPOT, MHC tetramers), with specificity and sensitivity roughly ranging from 60-90% (32,33). Although progress has been made during recent years, there is no standardized T-cell assay readily available for clinical use so far.…”

Section: Suggested Algorithm For An Improved Classificationmentioning

confidence: 99%

Diabetes mellitus: in search of an improved classification and treatment algorithm

Cahn

2016

Revista Romana De Medicina De Laborator

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Our current clinical doctrine and practice is based upon a classification of diabetes which relies mainly on some clinical manifestations/criteria, rather than markers of the pathophysiological mechanisms of the disease. An improved classification based on such biological markers (i.e. of insulin resistance, beta cell dysfunction, autoimmunity) may assist in clinical decision and may offer the opportunity of an optimized therapeutic strategy. We address here some important questions that have not yet been clarified, e.g. which markers/indicators best define the main pathogenic mechanisms of the disease in a patient with diabetes and what threshold values are relevant for this purpose.

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Biomarkers in type 1 diabetes

Cited by 15 publications

References 53 publications

Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes

Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes

Antigen-Specific Regulatory T Cells and Low Dose of IL-2 in Treatment of Type 1 Diabetes

Diabetes mellitus: in search of an improved classification and treatment algorithm

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