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- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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- Delli, Ahmed, et al.
(författare)
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Autoimmune type 1 diabetes.
- 2010
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Ingår i: Textbook of Diabetes. - : Wiley. - 9781405191814 ; , s. 141-152
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Bokkapitel (refereegranskat)abstract
- The pathophysiologic mechanisms in type 1 diabetes (T1DM) involve loss of islet β-cell secretory function caused by selective killing of these cells primarily by aggressive autoimmune responses involving both cellular and humoral immune pathways. Inflammatory cells heavily infiltrate pancreatic islets leading to insulitis where CD8+ T lymphocytes are thought to be responsible for selective and specific killing of β-cells. The complex etiology of T1DM involves a strong genetic predisposition, mainly human leukocyte antigen class II genes, and several putative environmental factors, which are thought to trigger autoimmunity or progression to clinical T1DM. A preclinical prodrome in T1DM may vary in duration in which one or more islet autoantibodies may precede insulitis and predict the disease at the early stages of pathologic insult. In genetically susceptible individuals with islet autoantibodies, metabolic indicators such as insulin release abnormalities and insulin resistance may best predict T1DM especially near clinical onset. Based on the improving understanding of the etiopathogenesis of T1DM, several clinical trials have been launched aiming at halting the autoimmunity responses, retarding disease progression or preserving remaining β-cell function after clinical onset.
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- Larsson, Helena, et al.
(författare)
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Future drug treatment of Type 1 diabetes
- 2010
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Ingår i: Textbook of Diabetes. - : Wiley. - 9781405191814 ; , s. 1001-1016
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Bokkapitel (refereegranskat)abstract
- Insulin replacement therapy is considered the only effective and feasible treatment for type 1 diabetes mellitus (T1DM) as only insulin is capable of reversing the metabolic disturbances and restoring a near - normal quality of life in patients with T1DM. Despite rigorous measures and major advances in health care provided for patients with T1DM, increased morbidity and mortality are still common from complications, which commonly develop within 10 – 12 years after clinical onset. Advances in the understanding of the natural history of T1DM and increased abilities to predict the disease have made it possible to design and implement prevention and intervention clinical trials. Clinical trials are aimed at: (a) preventing the initiation of islet autoimmunity (primary prevention);(b)reducing autoimmune β-cell killing and progression to clinical diabetes (secondary prevention); or(c)suppressing or modulating the immune response in order to halt β-cell killing and enhance β-cell regeneration (tertiary prevention or intervention). Several trials were implemented or are currently ongoing with dietary manipulation, parenteral or oral insulin or immune-suppressing or immune-modulating agents with the aim of preventing the disease or retarding its progression. The search for safe, effective and feasible drugs to prevent or cure T1DM is still ongoing. So far, immune modulation with alum - formulated GAD65 has been shown to be the most promising intervention to reduce the loss of β-cells. Anti-CD3 monocloncal autoantibodies also showed some benefits in patients with newly diagnosed T1DM.
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