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Journal ArticleDOI

An influence of HLA‐A, B, DR, DQ, and MICA on the occurrence of Celiac disease in patients with type 1 diabetes

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TLDR
A combined influence of alleles present in the MICA*008-B*08-A1-DR3-DQ2 extended haplotype on the development of CD in Slovenian individuals with T1D is suggested, where B*08 or/and a gene located close to it may play an important role, independently of HLA class II.
Abstract
Celiac disease (CD) is more common in individuals with insulin dependent diabetes mellitus (T1D) than in the general population. HLA class II molecules DQ8 (DQB1*0302-DQA1*0301) and DQ2 (DQB1*0201-DQA1*0501) have been identified as key genetic risk factors in both diseases. While DQ8 conveys a higher risk for T1D, DQ2 is more frequent in CD. Less is known about the contribution of HLA class I. The gut immune system has been implicated in the pathogenesis of both diseases. The MICA, which is mainly expressed in the gastrointestinal epithelium and recognized by gammadeltaT lymphocytes and natural killer (NK) cells via the NKG2D, might play a role. The aim of our study was to identify possible HLA class I and MICA alleles and conserved extended haplotypes as risk factors for the development of CD in T1D. Three groups consisting of 37 individuals with T1D and CD, 67 individuals with only T1D and 70 controls were analyzed. HLA class I and MICA alleles were determined using Luminex technology. An occurrence of CD in individuals with T1D was most significantly associated with B*08 (P = 7.3 x 10(-13)), contributing more than any of the HLA class II alleles (DRB1*0301, P = 5.00 x 10(-10); DQB1*0201, P = 7.65 x 10(-8)). Moreover, the association with CD became stronger when B*08(B*08-DQA*0501-DQB1*0201-DRB1*0301, P = 5.07 x 10(-12)) was present in the DRB1*0301-DQB1*0201-DQA1*0501 (P = 5.00 x 10(-10)) extended haplotype. We suggest a combined influence of alleles present in the MICA*008-B*08-A1-DR3-DQ2 extended haplotype on the development of CD in Slovenian individuals with T1D, where B*08 or/and a gene located close to it may play an important role, independently of HLA class II.

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Genetics, genomics, and evolutionary biology of NKG2D ligands

TL;DR: The molecular diversity ofNKG2DLs is reviewed, the increasing appreciation of their roles in a variety of medical conditions is discussed, and several explanations for the evolutionary force(s) that seem to drive the multiplicity and diversity of NKG2 DLs while maintaining their interaction with a single invariant receptor are proposed.
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Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM)

TL;DR: The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM.
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Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents.

TL;DR: The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T2DM, and present suggestions concerning screening tests.
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Shared genetics in coeliac disease and other immune-mediated diseases.

TL;DR: Shared genetics in coeliac disease and other immune‐mediated diseases (Symposium) and the role of EMTs in these diseases is discussed.
References
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Journal ArticleDOI

Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA

TL;DR: An activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses is defined.
Journal ArticleDOI

Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study

TL;DR: If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70%.
Journal ArticleDOI

Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial γδ T Cells

TL;DR: In this paper, the expression and recognition of a major histocompatibility complex (MHC) class I-related molecule, MICA, matches this localization, and the closely related MICB were recognized by intestinal epithelial T cells expressing diverse Vδ1 γδ TCRs.
Journal ArticleDOI

Coeliac disease: dissecting a complex inflammatory disorder

TL;DR: This dissection of the pathogenic mechanisms of coeliac disease has uncovered principles that are relevant to other chronic inflammatory diseases.
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