Immunologic and Metabolic Biomarkers of  -Cell Destruction in the Diagnosis of Type 1 Diabetes

Lebastchi, Jasmin; Herold, Kevan C.

doi:10.1101/cshperspect.a007708

Cited by 45 publications

(27 citation statements)

References 52 publications

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“…However, these autoantibodies are rarely detectable in children before 6 months of age (34). Moreover, the diagnostic sensitivity of the single autoantibody measurement in T1D patients is as low as 59-67% (35). To capture the therapeutic window for this disease, identifying new biomarkers for detection of early immunological events that affect human islets is critically important.…”

Section: Discussionmentioning

confidence: 99%

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

et al. 2014

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Type 1 diabetes (T1D) is an autoimmune disease resulting from the self-destruction of insulin-producing β-cells. Reduced neutrophil counts have been observed in patients with T1D. However, the pathological roles of neutrophils in the development of T1D remain unknown. Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both of which are neutrophil serine proteases stored in neutrophil primary granules, were markedly elevated in patients with T1D, especially those with disease duration of less than 1 year. Furthermore, circulating NE and PR3 levels increased progressively with the increase of the positive numbers and titers of the autoantibodies against β-cell antigens. An obvious elevation of NE and PR3 was detected even in those autoantibody-negative patients. Increased NE and PR3 in T1D patients are closely associated with elevated formation of neutrophil extracellular traps. By contrast, the circulating levels of α1-antitrypsin, an endogenous inhibitor of neutrophil serine proteases, are decreased in T1D patients. These findings support an early role of neutrophil activation and augmented neutrophil serine proteases activities in the pathogenesis of β-cell autoimmunity and also suggest that circulating NE and PR3 may serve as sensitive biomarkers for the diagnosis of T1D.

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Section: Discussionmentioning

confidence: 99%

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

et al. 2014

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“…As a result, inclusion of ELISpot as an endpoint in T1D studies is mainly limited to use in studies with HLA-DR4+ subjects [93,95]. In addition, the high sensitivity of the assay may affect both the inter-and intra-assay reproducibility.…”

Section: Elispot and Fluorospotmentioning

confidence: 95%

Immunotherapies and immune biomarkers in Type 1 diabetes: A partnership for success

Rekers

Herrath

Wesley

2015

Clinical Immunology

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The standard of care (SoC) for Type 1 diabetes (T1D) today is much the same as it was in the early 1920s, simply with more insulin options-fast-acting, slow-acting, injectable, and inhalable insulins. However, these well-tolerated treatments only manage the symptoms and complications, but do nothing to halt the underlying immune response. There is an unmet need for better treatment options for T1D that address all aspects of the disease. For decades, we have successfully treated T1D in preclinical animal models with immune-modifying therapies that have not demonstrated comparable efficacy in humans. The path to bringing such options to the clinic will depend on the implementation and standard inclusion of biomarkers of immune and therapeutic efficacy in T1D clinical trials, and dictate if we can create a new SoC that treats the underlying autoimmunity as well as the symptoms it causes.

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“…Furthermore, the endogenous pancreatic islets are dispersed throughout the pancreas and constitute only 2-3 % of the pancreatic volume [13][14][15]. Lack of specific validated markers on beta-cell surface that could be targeted by contrast agents add to the complexity of this endeavor.…”

Section: In Vivo Imaging Of Endogenous Bcmmentioning

confidence: 99%

Translational Molecular Imaging of Diabetes

Wang

Moore

2013

Curr Radiol Rep

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Diabetes mellitus contributes to significant morbidity and mortality worldwide. Translational medicine and research facilitate the transition of in vitro and experimental animal research to human applications. Molecular imaging is one of the powerful tools for translational research in diabetes, which accelerates transition of laboratory hypotheses into the clinic. These imaging tools are also instrumental for furthering our understanding about the causes that trigger diabetes and facilitate its progression. Imaging of therapeutic response is yet another avenue that can be explored in our attempt to find a cure for this disease. In this review we briefly summarize molecular imaging studies that show promise for clinical translation. Emphasis is placed on imaging of endogenous and transplanted beta cell mass, including application of various imaging modalities and approaches. Finally, the review attempts to define the future role of these non-invasive imaging techniques in diabetes research and clinical care.

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Immunologic and Metabolic Biomarkers of -Cell Destruction in the Diagnosis of Type 1 Diabetes

Cited by 45 publications

References 52 publications

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

Immunotherapies and immune biomarkers in Type 1 diabetes: A partnership for success

Translational Molecular Imaging of Diabetes

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