Association of high-affinity autoantibodies with type 1 diabetes high-risk HLA haplotypes

2021 ◽  
Author(s):  
Taylor M Triolo ◽  
Laura Pyle ◽  
Hali Broncucia ◽  
Taylor Armstrong ◽  
Liping Yu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Autoimmunity ◽  
Initial Visit ◽  
Prevention Study ◽  
High Affinity ◽  
Z Scores ◽  
Hla Haplotypes ◽  
Hla Dr3

Abstract Objective ECL assays are high-affinity autoantibody (Ab) tests that are more specific than Abs detected by traditional radiobinding assays (RBA) for risk screening and prediction of progression to type 1 diabetes. We sought to characterize the association of high-risk HLA haplotypes and genotypes with electrochemiluminescence (ECL) positivity and levels in relatives of individuals with type 1 diabetes. Methods We analyzed 602 participants from the TrialNet Pathway to Prevention Study who were positive for at least one RBA diabetes related Ab (GADA or IAA) and for whom ECL and HLA data were available. ECL and RBA Ab levels were converted to SD units away from mean (Z-scores) for analyses. Results Mean age at initial visit was 19.4+13.7 years; 344 (57.1%) were female and 104 (17.3%) carried the high-risk HLA- DR3/4*0302 genotype. At initial visit 424/602 (70.4%) participants were positive for either ECL-GADA or ECL-IAA, and 178/602 (29.6%) were ECL negative. ECL and RBA-GADA positivity were associated with both HLA-DR3 and DR4 haplotypes (all p<0.05), while ECL and RBA-GADA z-score titers were higher in participants with HLA-DR3 haplotypes only (both p<0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 haplotype (p<0.05). Conclusions ECL-GADA positivity is associated with the HLA-DR3 and HLA-DR4 haplotypes and levels are associated with the HLA-DR3 haplotype. ECL-IAA positivity is associated with HLA-DR4 haplotype. These studies further contribute to the understanding of genetic risk and islet autoimmunity endotypes in type 1 diabetes.

Interleukin-12p40 gene (IL-12B) polymorphism and Type 1 diabetes mellitus in Japanese: Possible role in subjects without having high-risk HLA haplotypes

2006 ◽  
Vol 71 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Jian Mei Yang ◽  
Shoichiro Nagasaka ◽  
Toshimitsu Yatagai ◽  
Tomoatsu Nakamura ◽  
Ikuyo Kusaka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
High Risk ◽  
Type 1 Diabetes Mellitus ◽  
Hla Haplotypes

High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease

Autoimmunity ◽  
2016 ◽  
Vol 49 (4) ◽  
pp. 240-247 ◽  
Author(s):  
Darja Smigoc Schweiger ◽  
Andrijana Mendez ◽  
Sabina Kunilo Jamnik ◽  
Nina Bratanic ◽  
Natasa Bratina ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
High Risk ◽  
Hla Dr3

The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes

The Lancet ◽  
2004 ◽  
Vol 364 (9446) ◽  
pp. 1699-1700 ◽  
Author(s):  
Kathleen M Gillespie ◽  
Steven C Bain ◽  
Anthony H Barnett ◽  
Polly J Bingley ◽  
Michael R Christie ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Rising Incidence ◽  
Hla Haplotypes ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type

scholarly journals Telomere Length is Not a Main factor for the Development of Islet Autoimmunity and Type 1 Diabetes in the TEDDY Study

2021 ◽  
Author(s):  
Hemang Parikh ◽  
Carina Törn ◽  
Xiang Liu ◽  
Suna Onengut-Gumuscu ◽  
Kevin Counts ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Telomere Length ◽  
Significant Negative Correlation ◽  
Paternal Age ◽  
Islet Autoimmunity ◽  
Degree Relative ◽  
High Prevalence ◽  
Nested Case Control ◽  
Hla Dr3

Abstract The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 children, 3-4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1,119 children in a nested case-control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter. The estimated median telomere length was 5.10 kb (IQR: 4.52 kb – 5.68 kb) using Computel. The age when the blood sample was drawn had a significant negative correlation with telomere length (P = 0.003). European children, particularly those from Finland (P = 0.041) and from Sweden (P = 0.001), had shorter telomeres than children from the U.S.A. Paternal age (P = 0.019) was positively associated with telomere length. First degree relative status, presence of gestational diabetes in the mother, and maternal age did not have a significant impact on estimated telomere length. HLA-DR4/4 or HLA-DR4/X children had significantly longer telomeres compared to children with HLA-DR3/3 or HLA-DR3/9 haplogenotypes (P = 0.008). Estimated telomere length was not significantly different with respect to any IA (P = 0.377), IAA-first (P = 0.248), GADA-first (P = 0.248) or T1D (P = 0.861). These results suggest that telomere length has no major impact on the risk for IA, the first step to develop T1D. Nevertheless, telomere length was shorter in the T1D high prevalence populations, Finland and Sweden.

scholarly journals Effects of Non-HLA Gene Polymorphisms on Development of Islet Autoimmunity and Type 1 Diabetes in a Population With High-Risk HLA-DR,DQ Genotypes

Diabetes ◽  
2012 ◽  
Vol 61 (3) ◽  
pp. 753-758 ◽  
Author(s):  
A. K. Steck ◽  
R. Wong ◽  
B. Wagner ◽  
K. Johnson ◽  
E. Liu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Gene Polymorphisms ◽  
Islet Autoimmunity ◽  
Hla Dr

scholarly journals Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes – Type 1 Diabetes Prediction and Prevention Study (DIPP)

2018 ◽  
Author(s):  
Santosh Lamichhane ◽  
Linda Ahonen ◽  
Thomas Sparholt Dyrlund ◽  
Esko Kemppainen ◽  
Heli Siljander ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Type ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Prevention Study ◽  
At Risk Children ◽  
Prediction And Prevention ◽  
Diabetes Prediction

AbstractType 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.

scholarly journals Do Non-HLA Genes Influence Development of Persistent Islet Autoimmunity and Type 1 Diabetes in Children With High-Risk HLA-DR,DQ Genotypes?

Diabetes ◽  
2009 ◽  
Vol 58 (4) ◽  
pp. 1028-1033 ◽  
Author(s):  
A. K. Steck ◽  
W. Zhang ◽  
T. L. Bugawan ◽  
K. J. Barriga ◽  
A. Blair ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Autoimmunity ◽  
Hla Genes ◽  
Hla Dr
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