ArticleDiabetologia2005
The effect of HLA class II, insulin and CTLA4 gene regions on the development of humoral beta cell autoimmunity.
Article in Diabetologia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- The role of islet autoantigen-specific T cells in the onset and treatment of type 1 diabetes mellitus.Frontiers in immunology · 2024Review
- A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss.Frontiers in immunology · 2023Article
- The Multifactorial Progression from the Islet Autoimmunity to Type 1 Diabetes in Children.International journal of molecular sciences · 2021Review
- Article
- What has zinc transporter 8 autoimmunity taught us about type 1 diabetes?Diabetologia · 2019Review
- The Relationship between insulin variable number of tandem repeats (INS-VNTR) -23 A/T and cytotoxic Tlymphocyte associated protein-4 (CTLA-4) +49 A/G polymorphisms with islet autoantibodies in persons with diabetes.Medical journal of the Islamic Republic of Iran · 2017Article
- Analysis of DLA-DQB1 and polymorphisms in CTLA4 in Cocker spaniels affected with immune-mediated haemolytic anaemia.Canine genetics and epidemiology · 2015Article
- Patterns of β-cell autoantibody appearance and genetic associations during the first years of life.Diabetes · 2013Article
- Influence of type 1 diabetes genes on disease progression: similarities and differences between countries.Current diabetes reports · 2012Review
- Effect of the PTPN22 and INS risk genotypes on the progression to clinical type 1 diabetes after the initiation of β-cell autoimmunity.Diabetes · 2012Article
- Novel gene associations in type 1 diabetes.Current diabetes reports · 2010Article
- Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.Genes and immunity · 2010Article
- Article
- Environmental factors and primary prevention in type 1 diabetes.Pediatric endocrinology, diabetes, and metabolism · 2009Article
- IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.Genes and immunity · 2007Article
- Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes.Diabetologia · 2006Article
- Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function.Diabetologia · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe aim of this study was to explore the contribution of genetic factors to the emergence of beta-cell-specific humoral autoimmunity. SUBJECTS AND
methodsWe analysed the effect of HLA class II, insulin (INS; -23 HphI variant) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4 [+49 and CT60]) genes on the appearance of beta-cell-specific autoantibodies in a large population-based birth cohort recruited in Finland. Infants carrying increased risk HLA DQB1 genotypes were monitored for the appearance of autoantibodies (islet cell autoantibodies [ICA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA] and islet antigen 2 antibodies [IA-2A]). Those who developed beta-cell-specific autoantibodies were studied (n=574, mean follow-up time: 4.9 years; range 0.5-9.3).
resultsIAA emerged at a higher rate in children with the -23 HphI AA INS genotype than in those carrying AT or TT variants (hazard ratio 2.1, 95% CI 1.4-2.9, p<0.001). This effect of the INS locus was present in both HLA DQB1 risk groups. The appearance of IAA showed a strong association also with the HLA DRB1*0401 allele (hazard ratio 13.1, 95% CI 1.8-93.4, p<0.001). The development of IA-2A was also somewhat accelerated by the DRB1*0401 variant (p=0.03). Isolated ICA positivity was independent of the HLA and INS genotypes. None of the humoral immune markers showed association with the CTLA4 gene. CONCLUSIONS/
interpretationThe INS and the DRB1 loci appear to contribute to the pathogenesis of type 1 diabetes by initiating/modifying insulin-specific autoimmunity. The emergence of IAA represents a crucial step in the development of beta cell autoimmunity in young children, in whom the appearance of GADA and IA-2A is linked to IAA.
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.