ArticleProceedings of the National Academy of Sciences of the United States of America1996
IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 245 citations in OpenAlex.
- Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.Diabetes care · 2011Guideline
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Molecular Portrait of Autoantigens in Type 1 Diabetes.Biomolecules · 2025Review
- Intertwined and unequal causality of type 1 diabetes and autoimmune thyroid disease: Insights from Mendelian randomization.Medicine · 2025Article
- Islet Autoantibodies to Pancreatic Insulin-Producing Beta Cells in Adolescent and Adults with Type 1 Diabetes Mellitus: A Cross-Sectional Study.Diagnostics (Basel, Switzerland) · 2023Article
- Immunoreactivities Against Different Tyrosine-Phosphatase 2 (IA-2)(256-760) Protein Domains Characterize Distinct Phenotypes in Subjects With LADA.Frontiers in endocrinology · 2022Article
- DNA methylation profiles in the blood of newborn term infants born to mothers with obesity.PloS one · 2022Article
- Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens.Virchows Archiv : an international journal of pathology · 2021Article
- Role of Receptor Protein Tyrosine Phosphatases (RPTPs) in Insulin Signaling and Secretion.International journal of molecular sciences · 2021Review
- Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis.Diabetes · 2021Article
- DNA methylation of individual repetitive elements in hepatitis C virus infection-induced hepatocellular carcinoma.Clinical epigenetics · 2019Article
- Review
- Environmental Factors Contribute to β Cell Endoplasmic Reticulum Stress and Neo-Antigen Formation in Type 1 Diabetes.Frontiers in endocrinology · 2017Article
- Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application.BMC biotechnology · 2016Article
- Validation of a rapid type 1 diabetes autoantibody screening assay for community-based screening of organ donors to identify subjects at increased risk for the disease.Clinical and experimental immunology · 2016Article
- Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.Internal and emergency medicine · 2016Article
- Discovery of Phosphorylated Peripherin as a Major Humoral Autoantigen in Type 1 Diabetes Mellitus.Cell chemical biology · 2016Article
- Pathophysiologic changes in IA-2/IA-2β null mice are secondary to alterations in the secretion of hormones and neurotransmitters.Acta diabetologica · 2016Article
- PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling.The EMBO journal · 2016Article
- The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB.Acta diabetologica · 2015Article
4 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
Abstract
IA-2 is a 105,847 Da transmembrane protein that belongs to the protein tyrosine phosphatase family. Immunoperoxidase staining with antibody raised against IA-2 showed that this protein is expressed in human pancreatic islet cells. In this study, we expressed the full-length cDNA clone of IA-2 in a rabbit reticulocyte transcription/translation system and used the recombinant radiolabeled IA-2 protein to detect autoantibodies by immunoprecipitation. Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. Sixty-six percent of the sera from patients, but none of the sera from controls, reacted with IA-2. The same diabetic sera tested for autoantibodies to islet cells (ICA) by indirect immunofluorescence and glutamic acid decarboxylase (GAD65Ab) by depletion ELISA showed 68% and 52% positivity, respectively. Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. Moreover, greater than 90% (14 of 15) of the ICA-positive but GAD65Ab-negative sera had autoantibodies to IA-2. Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening.
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