ArticleDiabetes2014
Molecular signatures differentiate immune states in type 1 diabetic families.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study.Scientific reports · 2022Trial
- In-vivo assessment of T cell kinetics in individuals at risk for type 1 diabetes.Clinical and experimental immunology · 2020Trial
- Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.European journal of immunology · 2016Trial
- Age-independent immune subtypes in type 1 diabetes exhibit distinct post-onset progression rates and immunotherapeutic responses.Diabetologia · 2026Article
- Molecular inflammatory expression profiles associated with the frequency of pain in individuals with sickle cell disease.Blood advances · 2025Article
- Type 1 diabetes presenting in adults: Trends, diagnostic challenges and unique features.Diabetes, obesity & metabolism · 2025Review
- Placental and Cord Blood DNA Methylation Changes Associated With Gestational Diabetes Mellitus in a Marginalized Population: The Untold Role of Saturated Fats.Molecular nutrition & food research · 2025Article
- CRISPR-GEM: A Novel Machine Learning Model for CRISPR Genetic Target Discovery and Evaluation.ACS synthetic biology · 2024Article
- CRISPR-GEM: A Novel Machine Learning Model for CRISPR Genetic Target Discovery and Evaluation.bioRxiv : the preprint server for biology · 2024Article
- Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression.Science advances · 2024Article
- Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review.Communications medicine · 2024Article
- Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.Genome medicine · 2024Article
- The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes.Scientific reports · 2023Article
- RNA Sequencing Analysis of CD4Critical care explorations · 2023Article
- Genetic determinants of type 1 diabetes in individuals with weak evidence of islet autoimmunity at disease onset.Diabetologia · 2023Article
- Clinical and experimental treatment of type 1 diabetes.Clinical and experimental immunology · 2022Review
- Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.Scientific reports · 2021Article
- Auto-antigen and Immunomodulatory Agent-Based Approaches for Antigen-Specific Tolerance in NOD Mice.Current diabetes reports · 2021Review
- Article
- Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes.Diabetologia · 2020Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Mechanisms associated with type 1 diabetes (T1D) development remain incompletely defined. Using a sensitive array-based bioassay where patient plasma is used to induce transcriptional responses in healthy leukocytes, we previously reported disease-specific, partially interleukin (IL)-1-dependent signatures associated with preonset and recent onset (RO) T1D relative to unrelated healthy control subjects (uHC). To better understand inherited susceptibility in T1D families, we conducted cross-sectional and longitudinal analyses of healthy autoantibody-negative (AA(-)) high HLA-risk siblings (HRS) (DR3 and/or DR4) and AA(-) low HLA-risk siblings (LRS) (non-DR3/non-DR4). Signatures, scored with a novel ontology-based algorithm, and confirmatory studies differentiated the RO T1D, uHC, HRS, and LRS plasma milieus. Relative to uHC, T1D family members exhibited an elevated inflammatory state, consistent with innate receptor ligation that was independent of HLA, AA, or disease status and included elevated plasma IL-1α, IL-12p40, CCL2, CCL3, and CCL4 levels. Longitudinally, signatures of T1D progressors exhibited increasing inflammatory bias. Conversely, HRS possessing decreasing AA titers revealed emergence of an IL-10/transforming growth factor-β-mediated regulatory state that paralleled temporal increases in peripheral activated CD4(+)/CD45RA(-)/FoxP3(high) regulatory T-cell frequencies. In AA(-) HRS, the familial innate inflammatory state also was temporally supplanted by immunoregulatory processes, suggesting a mechanism underlying the decline in T1D susceptibility with age.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.