scholarly journals HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in north-western Mexico

2015 ◽  
Vol 80 (2) ◽  
pp. 135-143
Author(s):  
M.E. Mejía-León ◽  
K.M. Ruiz-Dyck ◽  
A.M. Calderón de la Barca
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Genetic Risk ◽  
Western Mexico ◽  
Hla Dq ◽  
North Western

Genetic risk for co-occurrence of type 1 diabetes and celiac disease is modified by HLA-C and killer immunoglobulin-like receptors

2014 ◽  
Vol 84 (5) ◽  
pp. 471-478 ◽  
Author(s):  
D. Smigoc Schweiger ◽  
A. Mendez ◽  
S. Kunilo Jamnik ◽  
N. Bratanic ◽  
N. Bratina ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Genetic Risk

scholarly journals On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes

2012 ◽  
Vol 14 ◽  
Author(s):  
Robert Busch ◽  
Alessandra De Riva ◽  
Andreas V. Hadjinicolaou ◽  
Wei Jiang ◽  
Tieying Hou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Mhc Class Ii ◽  
Human Leukocyte ◽  
Peptide Binding Specificity ◽  
Risk Alleles ◽  
Hla Dq ◽  
Peptide Loading ◽  
Underlying Mechanisms

This review discusses mechanisms that link allelic variants of major histocompatibility complex (MHC) class II molecules (MHCII) to immune pathology. We focus on HLA (human leukocyte antigen)-DQ (DQ) alleles associated with celiac disease (CD) and type 1 diabetes (T1D) and the role of the murine DQ-like allele, H2-Ag7 (I-Ag7 or Ag7), in murine T1D. MHCII molecules bind peptides, and alleles vary in their peptide-binding specificity. Disease-associated alleles permit binding of disease-inducing peptides, such as gluten-derived, Glu-/Pro-rich gliadin peptides in CD and peptides from islet autoantigens, including insulin, in T1D. In addition, the CD-associated DQ2.5 and DQ8 alleles are unusual in their interactions with factors that regulate their peptide loading, invariant chain (Ii) and HLA-DM (DM). The same alleles, as well as other T1D DQ risk alleles (and Ag7), share nonpolar residues in place of Asp at β57 and prefer peptides that place acidic side chains in a pocket in the MHCII groove (P9). Antigen-presenting cells from T1D-susceptible mice and humans retain CLIP because of poor DM editing, although underlying mechanisms differ between species. We propose that these effects on peptide presentation make key contributions to CD and T1D pathogenesis.

scholarly journals HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, are More Expressed Than Non-Predisposing Alleles and are Coordinately Regulated

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 751 ◽  
Author(s):  
Farina ◽  
Picascia ◽  
Pisapia ◽  
Barba ◽  
Vitale ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Cd4 T Cells ◽  
High Expression ◽  
Transcriptional Level ◽  
Risk Alleles ◽  
Hla Dq ◽  
Hla Dqa1

HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.

Sa1331 HLA-DQ Genotype Distribution in Type 1 Diabetes Mellitus Patients With Concomitant Celiac Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-274-S-275
Author(s):  
Sjoerd Feitze Bakker ◽  
Maarten E. Tushuizen ◽  
J. Bart A. Crusius ◽  
Suat Simsek ◽  
Chris J. Mulder ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Type 1 Diabetes Mellitus ◽  
Genotype Distribution ◽  
Hla Dq

HLA-DQ types of celiac disease in Libyan children with type 1 diabetes mellitus

2012 ◽  
Vol 24 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Millad Ghawil ◽  
Valeria Miotti ◽  
Elio Tonutti ◽  
Alfred Tenore ◽  
Ibtisam Hadeed ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Type 1 Diabetes Mellitus ◽  
Hla Dq

scholarly journals Prevalence of obesity was related to HLA-DQ in 2–4-year-old children at genetic risk for type 1 diabetes

2014 ◽  
Vol 38 (12) ◽  
pp. 1491-1496 ◽  
Author(s):  
J Yang ◽  
◽  
Å Lernmark ◽  
U M Uusitalo ◽  
K F Lynch ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Hla Dq ◽  
Prevalence Of Obesity

scholarly journals Prediction of autoimmune diabetes and celiac disease in childhood by genes and perinatal environment: Design and initial aims of the PAGE study

2014 ◽  
Vol 24 (1-2) ◽  
Author(s):  
Lars C. Stene ◽  
Geir Joner ◽  
Ketil Størdal
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Blood Plasma ◽  
Genetic Risk ◽  
Autoimmune Diabetes ◽  
Genetic Risk Factors ◽  
Host Cells ◽  
Full Cohort

Type 1 diabetes and celiac disease result from misdirected immune mediated destruction of host cells, and are among the most common chronic diseases in children. Despite changes in incidence over the past 3 decades, little is known about non-genetic risk factors (except for dietary gluten for celiac disease). Norway is among the countries in the world with the highest incidence of these two diseases. We describe here plans and study design for the PAGE study (Prediction of Autoimmune diabetes and celiac disease in childhood by Genes and perinatal Environment). PAGE is a sub-study within the Norwegian Mother and Child Cohort study, including follow-up of more than 100,000 pregnancies. Children who develop type 1 diabetes or celiac disease are identified via linkage to the Norwegian Patient Register and the Norwegian Childhood Diabetes Registry, with complementing information from questionnaires. The overall aim is to test hypotheses about potential non-genetic risk factors for type 1 diabetes and for celiac disease, with focus on factors operating early in life. In addition to a full cohort analysis of factors registered in questionnaires, we will analyse biomarkers in maternal blood plasma and cord blood plasma. Mothers and children will be genotyped for well-established susceptibility polymorphisms. Biomarkers will be analysed in cases and controls within the cohort. Factors to be tested in the full cohort include infant feeding, diet and dietary supplements in the mother during pregnancy and in the child, and use of antibiotics and non-prescription drugs. Biomarkers to be tested include 25-hydroxyvitamin D, markers of immune activation, and small metabolites (metabolomics). We will also explore the potential role of maternal cells in the fetal circulation (maternal microchimerism) in later risk of celiac disease and type 1 diabetes.

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