Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KIRs (killer Ig-like receptors) expressed on natural killer (NK) cells are an important component of innate (and adaptive) immunity. They are either activatory or inhibitory, and certain KIRs are known to interact with specific motifs of HLA Class I molecules, which is very crucial in determining whether a cell is targeted to lysis or otherwise. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with an adult onset (>30 years). Because autoantibodies and autoimmunity involved are involved in the etiology of LADA, KIRs might play an important role in conferring susceptibility to or protection against the disease. The purpose of this study was to identify killer immunoglobulin-like receptor (KIR) genes, which are associated with susceptibility to and protection against type 1 diabetes in Latvian and Asian Indian patients with LADA. KIR and HLA-C ligand genotyping was performed using PCR-SSP in LADA patients from Latvia (n= 45) with age- and sex-matched controls (n= 92) and from India (n= 86) with controls (n= 98). Results showed that in Latvian patients with LADA, KIRs 2DL1, 2DS2, and 2DS4 were associated with susceptibility and KIR 2DS5 with protection. In Asian Indian LADA patients, KIRs 2DL5 and 3DL1 were associated with susceptibility and KIRs 2DS1 and 2DS3 with protection. Stratification analyses for KIRs that bind to HLA-C1 and C2 were performed. We concluded that KIRs are important in conferring susceptibility (or protection) to adult patients with LADA in both our study populations. However the KIR genes (and their HLA-C ligands) conferring susceptibility or protection in these two populations differ, showing a role of ethnicity in disease susceptibility.
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PMID:Different KIRs confer susceptibility and protection to adults with latent autoimmune diabetes in Latvian and Asian Indian populations. 1912 Feb 81

Most cases of type 1 diabetes mellitus (T1DM) are caused by an autoimmune reaction, involving genetic and environmental factors, which ultimately disrupt insulin-producing pancreatic beta cells. Several genes, including those encoding human leukocyte antigen (HLA) class II (IDDM1 locus), insulin (IDDM2 locus), and cytotoxic T lymphocyte antigen (CTLA) 4 (IDDM12 locus), are involved in this process. In this paper, I review the studies of Japanese patients with childhood type 1A diabetes mellitus (T1ADM), including the results of the multicenter study conducted by The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). The JSGIT study analyzed the HLA-DRB1, DQB1, DPB1, A, C, and B genes in Japanese patients with childhood T1ADM to identify candidate genes specific for Japanese individuals. Some of the genes were also involved in diabetes in Caucasian. A comparison of parents and siblings showed that several susceptible DRB1-DQB1 haplotypes and resistant alleles were involved in the development of T1ADM. However, results of transmission disequilibrium tests demonstrated no genomic imprinting of HLA Class I or II genes in Japanese patients. The frequency of the DRB1*09:01 allele was significantly higher in patients who developed the disease at 2-5 years old than in other patients. Identifying HLA gene polymorphisms may help to examine the relationship between antigen-presenting molecule structures and autoantigenic peptides. The JSGIT study also identified single nucleotide polymorphisms in genes other than HLA. Understanding the genetic factors associated with T1ADM that help explain the lower incidence of this disease in Japanese than in Caucasian individuals, will help us to elucidate its pathogenesis.
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PMID:Genetic susceptibility of childhood type 1 diabetes mellitus in Japan. 2333 Feb 47

Available evidence provides arguments both for and against a primary pathogenic role for T cells in human type 1 diabetes. Genetic susceptibility linked to HLA Class II lends strong support. Histopathology documents HLA Class I hyperexpression and islet infiltrates dominated by CD8+ T cells. While both hallmarks are near absent in autoantibody-positive donors, the variable insulitis and residual beta cells of recent-onset donors suggests the existence of a younger-onset endotype with more aggressive autoimmunity and an older-onset endotype with more vulnerable beta cells. Functional arguments from ex vivo and in vitro human studies and in vivo 'humanised' mouse models are instead neutral or against a T cell role. Clinical support is provided by the appearance of islet autoantibodies before disease onset. The faster C-peptide loss and superior benefits of immunotherapies in individuals with younger-onset type 1 diabetes reinforce the view of age-related endotypes. Clarifying the relative role of T cells will require technical advances in the identification of their target antigens, in their detection and phenotyping in the blood and pancreas, and in the study of the T cell/beta cell crosstalk. Critical steps toward this goal include the understanding of the link with environmental triggers, the description of T cell changes along the natural history of disease, and their relationship with age and the 'benign' islet autoimmunity of healthy individuals. Graphical abstract.
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PMID:Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset? 3308 70