Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age.


:The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive β-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4-CD8- cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed β-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that high IL32 in case samples was contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and β-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.






Kallionpää H,Somani J,Tuomela S,Ullah U,de Albuquerque R,Lönnberg T,Komsi E,Siljander H,Honkanen J,Härkönen T,Peet A,Tillmann V,Chandra V,Anagandula MK,Frisk G,Otonkoski T,Rasool O,Lund R,Lähdesmäki H,Knip M,Lahes




Has Abstract


2019-10-01 00:00:00
















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    abstract::Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and in...


    pub_type: 杂志文章


    authors: Sassy-Prigent C,Heudes D,Mandet C,Bélair MF,Michel O,Perdereau B,Bariéty J,Bruneval P

    更新日期:2000-03-01 00:00:00

  • Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

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    pub_type: 杂志文章


    authors: Lee HY,Lee JS,Alves T,Ladiges W,Rabinovitch PS,Jurczak MJ,Choi CS,Shulman GI,Samuel VT

    更新日期:2017-08-01 00:00:00

  • Selective downregulation of the high molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic subjects.

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    pub_type: 杂志文章


    authors: Basu R,Pajvani UB,Rizza RA,Scherer PE

    更新日期:2007-08-01 00:00:00

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    pub_type: 杂志文章


    authors: Mitchell BD,Cole SA,Comuzzie AG,Almasy L,Blangero J,MacCluer JW,Hixson JE

    更新日期:1999-09-01 00:00:00

  • Dissociation of intestinal and hepatic activities of FXR and LXRα supports metabolic effects of terminal ileum interposition in rodents.

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    authors: Mencarelli A,Renga B,D'Amore C,Santorelli C,Graziosi L,Bruno A,Monti MC,Distrutti E,Cipriani S,Donini A,Fiorucci S

    更新日期:2013-10-01 00:00:00

  • Tumor necrosis factor alpha: a key component of the obesity-diabetes link.

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    pub_type: 杂志文章,评审


    authors: Hotamisligil GS,Spiegelman BM

    更新日期:1994-11-01 00:00:00

  • Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

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    pub_type: 杂志文章


    authors: Li H,O'Meara M,Zhang X,Zhang K,Seyoum B,Yi Z,Kaufman RJ,Monks TJ,Wang JM

    更新日期:2019-06-01 00:00:00

  • Effects of gestational hyperglycemia on glucose metabolism and its hormonal control in the fasted, newborn rat during the early postnatal period.

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    pub_type: 杂志文章


    authors: Nurjhan N,Ktorza A,Ferre P,Girard JR,Picon L

    更新日期:1985-10-01 00:00:00

  • Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants.

    abstract::It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previou...


    pub_type: 临床试验,杂志文章


    authors: Butler PC,Kryshak EJ,Schwenk WF,Haymond MW,Rizza RA

    更新日期:1990-02-01 00:00:00

  • Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals.

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    pub_type: 杂志文章


    authors: Consitt LA,Bell JA,Koves TR,Muoio DM,Hulver MW,Haynie KR,Dohm GL,Houmard JA

    更新日期:2010-06-01 00:00:00

  • SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a.

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    pub_type: 杂志文章


    authors: Xu EE,Sasaki S,Speckmann T,Nian C,Lynn FC

    更新日期:2017-08-01 00:00:00

  • Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults.

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    pub_type: 杂志文章,随机对照试验


    authors: Johnson ML,Distelmaier K,Lanza IR,Irving BA,Robinson MM,Konopka AR,Shulman GI,Nair KS

    更新日期:2016-01-01 00:00:00

  • Diabetic patients without vascular complications display enhanced basal platelet activation and decreased antioxidant status.

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    pub_type: 杂志文章


    authors: Véricel E,Januel C,Carreras M,Moulin P,Lagarde M

    更新日期:2004-04-01 00:00:00

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    abstract::The macro- and microvascular burden of type 2 diabetes is well established. A number of recent single risk factor intervention trials targeting hyperglycemia, dyslipidemia, hypertension, procoagulation, microalbumuria, and existing cardiovascular disorders have, however, shown major beneficial effects on long-term out...


    pub_type: 杂志文章,评审


    authors: Gaede P,Pedersen O

    更新日期:2004-12-01 00:00:00

  • Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe.

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    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Zinman B,Kahn SE,Haffner SM,O'Neill MC,Heise MA,Freed MI,ADOPT Study Group.

    更新日期:2004-12-01 00:00:00

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    pub_type: 杂志文章,多中心研究


    authors: Palmer ND,Langefeld CD,Campbell JK,Williams AH,Saad M,Norris JM,Haffner SM,Rotter JI,Wagenknecht LE,Bergman RN,Rich SS,Bowden DW

    更新日期:2006-04-01 00:00:00

  • Metformin prevents the development of chronic heart failure in the SHHF rat model.

    abstract::Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomi...


    pub_type: 杂志文章


    authors: Cittadini A,Napoli R,Monti MG,Rea D,Longobardi S,Netti PA,Walser M,Samà M,Aimaretti G,Isgaard J,Saccà L

    更新日期:2012-04-01 00:00:00

  • Changing metabolic signatures of amino acids and lipids during the prediabetic period in a pig model with impaired incretin function and reduced β-cell mass.

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    pub_type: 杂志文章


    authors: Renner S,Römisch-Margl W,Prehn C,Krebs S,Adamski J,Göke B,Blum H,Suhre K,Roscher AA,Wolf E

    更新日期:2012-08-01 00:00:00

  • A Reg family protein is overexpressed in islets from a patient with new-onset type 1 diabetes and acts as T-cell autoantigen in NOD mice.

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    pub_type: 杂志文章


    authors: Gurr W,Yavari R,Wen L,Shaw M,Mora C,Christa L,Sherwin RS

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  • Central role for interleukin-2 in type 1 diabetes.

    abstract::Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...


    pub_type: 杂志文章,评审


    authors: Hulme MA,Wasserfall CH,Atkinson MA,Brusko TM

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  • Magnetic resonance imaging and computed tomography in long-term-functioning duct-occluded pancreas allotransplants.

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    pub_type: 杂志文章


    authors: Schlumpf R,Marincek B,Von Schulthess G,Decurtins M,Largiadèr F

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  • v- and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fat

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    pub_type: 杂志文章


    authors: Maier VH,Melvin DR,Lister CA,Chapman H,Gould GW,Murphy GJ

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  • Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

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    pub_type: 杂志文章,随机对照试验


    authors: Tong J,Davis HW,Summer S,Benoit SC,Haque A,Bidlingmaier M,Tschöp MH,D'Alessio D

    更新日期:2014-07-01 00:00:00

  • Report of the American Diabetes Association's Task Force on standardization of the insulin assay.

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    pub_type: 杂志文章


    authors: Robbins DC,Andersen L,Bowsher R,Chance R,Dinesen B,Frank B,Gingerich R,Goldstein D,Widemeyer HM,Haffner S,Hales CN,Jarett L,Polonsky K,Porte D,Skyler J,Webb G,Gallagher K

    更新日期:1996-02-01 00:00:00

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    pub_type: 杂志文章


    authors: Oeser JK,Parekh VV,Wang Y,Jegadeesh NK,Sarkar SA,Wong R,Lee CE,Pound LD,Hutton JC,Van Kaer L,O'Brien RM

    更新日期:2011-11-01 00:00:00

  • Sequence variation in PPARG may underlie differential response to troglitazone.

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    pub_type: 杂志文章,随机对照试验


    authors: Wolford JK,Yeatts KA,Dhanjal SK,Black MH,Xiang AH,Buchanan TA,Watanabe RM

    更新日期:2005-11-01 00:00:00

  • Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes.

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    pub_type: 杂志文章


    authors: McDuffie M,Maybee NA,Keller SR,Stevens BK,Garmey JC,Morris MA,Kropf E,Rival C,Ma K,Carter JD,Tersey SA,Nunemaker CS,Nadler JL

    更新日期:2008-01-01 00:00:00

  • Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell.

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    pub_type: 杂志文章


    authors: Martinez SC,Cras-Méneur C,Bernal-Mizrachi E,Permutt MA

    更新日期:2006-06-01 00:00:00

  • Diurnal variation in vascular and metabolic function in diet-induced obesity: divergence of insulin resistance and loss of clock rhythm.

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    pub_type: 杂志文章


    authors: Prasai MJ,Mughal RS,Wheatcroft SB,Kearney MT,Grant PJ,Scott EM

    更新日期:2013-06-01 00:00:00

  • Effect of combined antisense oligonucleotides against high-glucose- and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability.

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    pub_type: 杂志文章


    authors: Oshitari T,Polewski P,Chadda M,Li AF,Sato T,Roy S

    更新日期:2006-01-01 00:00:00