ArticleJCI insight2019
B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects.JCI insight · 2021Trial
- Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes.Nature immunology · 2020Trial
- In-vivo assessment of T cell kinetics in individuals at risk for type 1 diabetes.Clinical and experimental immunology · 2020Trial
- Phenotypic Analysis of Human Lymph Nodes in Subjects With New-Onset Type 1 Diabetes and Healthy Individuals by Flow Cytometry.Frontiers in immunology · 2019Trial
- Early-onset type 1 diabetes mellitus in a child with a pathogenicTranslational pediatrics · 2026Article
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- CXCR3 expression on antigen-experienced B cells is systemically dysregulated in type 1 diabetes.Diabetologia · 2026Article
- Stage 1 type 1 diabetes memory B lymphocytes transcriptionally differ from healthy controls and harbor insulin-binding specificities.ImmunoHorizons · 2025Article
- Type 1 Diabetes TrialNet: Leading the Charge in Disease Prediction, Prevention, and Immunotherapeutic Mechanistic Understanding.Diabetes care · 2025Review
- Blood samples collected under anesthesia can be used as a source of non-diseased controls for immune-based assays.Frontiers in immunology · 2025Article
- Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.Immunity · 2024Article
- Integrating Omics into Functional Biomarkers of Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.The Journal of experimental medicine · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes.Antibodies (Basel, Switzerland) · 2024Review
- Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.Genome medicine · 2024Article
- The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.Frontiers in immunology · 2024Article
- Abatacept increases T cell exhaustion in early RA individuals who carry HLA risk alleles.Frontiers in immunology · 2024Article
- Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.Communications medicine · 2023Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Costimulatory interactions control T cell activation at sites of activated antigen-presenting cells, including B cells. Blockade of the CD28/CD80/CD86 costimulatory axis with CTLA4Ig (abatacept) is widely used to treat certain autoimmune diseases. While transiently effective in subjects with new-onset type 1 diabetes (T1D), abatacept did not induce long-lasting immune tolerance. To elucidate mechanisms limiting immune tolerance in T1D, we performed unbiased analysis of whole blood transcriptomes and targeted measurements of cell subset levels in subjects from a clinical trial of abatacept in new-onset T1D. We showed that individual subjects displayed age-related immune phenotypes ("immunotypes") at baseline, characterized by elevated levels of B cells or neutrophils, that accompanied rapid or slow progression, respectively, in both abatacept- and placebo-treated groups. A more pronounced immunotype was exhibited by a subset of subjects showing poor response (resistance) to abatacept. This resistance immunotype was characterized by a transient increase in activated B cells (one of the cell types that binds abatacept), reprogrammed costimulatory ligand gene expression, and reduced inhibition of anti-insulin antibodies. Our findings identify immunotypes in T1D subjects that are linked to the rate of disease progression, both in placebo- and abatacept-treated subjects. Furthermore, our results suggest therapeutic approaches to restore immune tolerance in T1D.
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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.