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Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease.

ABSTRACT: Type 1 diabetes (T1D) is a chronic autoimmune disorder resulting from immune-mediated destruction of insulin-producing beta cells within the pancreatic islets. Prediction of T1D is now possible, as having 2 or more islet autoantibodies confers a 100% risk of diabetes development. With the ability to predict disease development, clinical trials to prevent diabetes onset have been completed and are currently under way. This review focuses on the natural history, prediction, and prevention trials in T1D. We review the lessons learned from these attempts at preventing a chronic autoimmune disease and apply the paradigm from T1D prevention to other autoimmune disorders.

SUBMITTER: Simmons K

PROVIDER: S-EPMC4250578 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease.

Simmons Kimber K Michels Aaron W AW

Rheumatic diseases clinics of North America 20140902 4

Type 1 diabetes (T1D) is a chronic autoimmune disorder resulting from immune-mediated destruction of insulin-producing beta cells within the pancreatic islets. Prediction of T1D is now possible, as having 2 or more islet autoantibodies confers a 100% risk of diabetes development. With the ability to predict disease development, clinical trials to prevent diabetes onset have been completed and are currently under way. This review focuses on the natural history, prediction, and prevention trials i ...[more]

PMID: 25437293

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Project description:Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*0302), tightly linked with DR3 and DR4, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms (or rare variants) of various genes, such as the cytotoxic T-lymphocyte- associated antigen (CTLA4), the protein tyrosine phosphatase non-receptor type 22 (PTPN22), the interleukin-2 Receptor (IL2Ra), the Vitamin D receptor (VDR), and the tumor-necrosis-factor-α (TNF) that are involved in immune regulation have been identified to confer susceptibility to both T1D and AITD. Other genes including cluster of differentiation 40 (CD40), the forkhead box P3 (FOXP3), the MHC Class I Polypeptide-Related Sequence A (MICA), insulin variable number of tandem repeats (INS-VNTR), the C-Type Lectin Domain Containing 16A (CLEC16A), the Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3) gene, the interferon-induced helicase C domain-containing protein 1 (IFIH1), and various cytokine genes are also under suspicion to increase susceptibility to T1D and AITD. Further, BTB domain and CNC homolog 2 (BACH2), C-C motif chemokine receptor 5 (CCR5), SH2B adaptor protein 3 (SH2B3), and Rac family small GTPase 2 (RAC2) are found to be associated with T1D and AITD by various independent genome wide association studies and overlap in our list, indicating a strong common genetic link for T1D and AITD. As several susceptibility genes and environmental factors contribute to the disease aetiology of both T1D and AITD and/or AP subtype III variant (T1D+AITD) simultaneously, all patients with T1D should be screened for AITD, and vice versa.

Dataset Information

Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease.

Publications

Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease.

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