ArticleThe Journal of clinical investigation2018
Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Open Label Pilot Study of the Effect of Methyldopa on MHC-II Antigen Presentation in Type 1 Diabetes
A Phase 1b, Randomized, Single-blind, Placebo-controlled, Multiple Ascending Dose (MAD) Study to Assess the Steady-State Pharmacokinetics and DQ8 Blocking Efficacy of Orally Administered IMT-002 in Patients With Type 1 Diabetes and HLA-DQ8
Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial.Diabetes care · 2021Trial
- Exploring MHC class II I-Ab blockade as a potential treatment for Sjögren's disease in the mouse model.ImmunoHorizons · 2025Article
- Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity.The Journal of clinical endocrinology and metabolism · 2025Observational
- Current perspectives and the future of disease-modifying therapies in type 1 diabetes.World journal of diabetes · 2025Article
- Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- Genetics and epigenetics of autoimmune thyroid diseases: Translational implications.Best practice & research. Clinical endocrinology & metabolism · 2023Review
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
- Autoantibody and T cell responses to oxidative post-translationally modified insulin neoantigenic peptides in type 1 diabetes.Diabetologia · 2023Article
- Novel approaches to the treatment of type 1 diabetes.Journal of diabetes · 2022Article
- Temporal development of T cell receptor repertoires during childhood in health and disease.JCI insight · 2022Article
- Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B.Circulation research · 2022Article
- Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes.The Journal of clinical endocrinology and metabolism · 2022Article
- Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes.International journal of molecular sciences · 2022Review
- Alpha-Methyldopa May Attenuate Insulin Demand in Women with Gestational Diabetes Treated with Betamethasone.Healthcare (Basel, Switzerland) · 2022Article
- Should Renal Inflammation Be Targeted While Treating Hypertension?Frontiers in physiology · 2022Review
- Blocking IAgLife sciences · 2022Article
- Diabetes type 1: Can it be treated as an autoimmune disorder?Reviews in endocrine & metabolic disorders · 2021Review
- The Role of Programmed Death-1 in Type 1 Diabetes.Current diabetes reports · 2021Review
- Auto-antigen and Immunomodulatory Agent-Based Approaches for Antigen-Specific Tolerance in NOD Mice.Current diabetes reports · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen-binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro, with 1 compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug with a similar structure, methyldopa, specifically blocked DQ8 in patients with recent-onset T1D and reduced inflammatory T cell responses to insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity.
Indexed as
Identifiers
What OpenQuestion holds
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.