The Role of Viruses and Environmental Factors in the Induction of Diabetes

Yoon, Jaeho

doi:10.1007/978-3-642-75741-9_6

Cited by 97 publications

(71 citation statements)

References 104 publications

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“…The HLA-DQ locus on chromosome 6p21 confers the strongest genetic risk for T1D (24). The majority of individuals with these genetic risk factors do not develop T1D and several environmental factors have been considered including infections (6,13,34,40), climate (35), diet (3,21), and stress (16). The possible influence of viral infections as a trigger of islet autoimmunity or clinical onset of T1D has been reported in numerous studies (5,19).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

et al. 2013

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Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA).LVAb at 75 th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4 th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4 th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X ( p < 0.0001). Furthermore, in the group with 4 th quartile LVAb, 55% were IAA positive ( p = 0.01) and correlation was found between 4 th quartile LVAb and IAA in children < 10 years of age ( p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4 th quartile LVAb correlated with IAA; and 3) there was a correlation between 4 th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.

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Section: Introductionmentioning

confidence: 99%

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

et al. 2013

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“…Furthermore, epidemiological studies have associated infections with many different viruses with autoimmune diseases like type 1 diabetes (T1D) (2)(3)(4)(5) and MS (6)(7)(8)(9). However, it is still unclear how these infectious agents would cause autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes

et al. 2004

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We document here that infection of prediabetic mice with a virus expressing an H-2K b -restricted mimic ligand to a self epitope present on β cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2K b -deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction.

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“…The process, which finally leads to complete beta-cell loss and onset of clinical disease, starts years before any clinical symptoms and is thought to result from several factors involving host genes, autoimmune responses and cytokines, as well as environmental factors. Results from previous cross-sectional and prospective studies on patients with Type 1 diabetes and/or prediabetic individuals have suggested that enterovirus infections are involved in the development of the disease [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15].…”

mentioning

confidence: 99%

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

Ylipaasto

Klingel

Lindberg³

et al. 2004

Diabetologia

265

248

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Aims/hypothesis. It is thought that enterovirus infections cause beta-cell damage and contribute to the development of Type 1 diabetes by replicating in the pancreatic islets. We sought evidence for this through autopsy studies and by investigating known enterovirus receptors in cultured human islets. Methods. Autopsy pancreases from 12 newborn infants who died of fulminant coxsackievirus infections and from 65 Type 1 diabetic patients were studied for presence of enteroviral ribonucleic acid by in situ hybridisation. Forty non-diabetic control pancreases were included in the study. The expression and role of receptor candidates in cultured human islets were investigated with receptor-specific antibodies using immunocytochemistry and functional assays. Results. Enterovirus-positive islet cells were found in some of both autopsy specimen collections, but not in control pancreases. No infected cells were seen in exocrine tissue. The cell surface molecules, poliovirus receptor and integrin αvβ 3 , which act as enterovirus receptors in established cell lines, were expressed in beta cells. Antibodies to poliovirus receptor, human coxsackievirus and adenovirus receptor and integrin αvβ 3 protected islets and beta cells from adverse effects of poliovirus, coxsackie B viruses, and several of the arginine-glycine-aspartic acid motifs containing enteroviruses and human parechovirus 1 respectively. No evidence was found for expression of the decay-accelerating factor which acts as a receptor for several isletcell-replicating echoviruses in established cell lines. Conclusions/interpretation. The results show a definite islet-cell tropism of enteroviruses in the human pancreas. Some enteroviruses seem to use previously identified cell surface molecules as receptors in beta cells, whereas the identity of receptors used by other enteroviruses remains unknown. [Diabetologia (2004) 47:225-239]

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The Role of Viruses and Environmental Factors in the Induction of Diabetes

Cited by 97 publications

References 104 publications

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

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