No evidence of enteroviruses in the intestine of patients with type 1 diabetes

Mercalli, Alessia; Lampasona, Vito; Klingel, Karin; Albarello, Luca; Lombardoni, Carlo; Ekström, Johanna; Sordi, Valeria; Bolla, Andrea Mario; Mariani, A.; Bzhalava, Davit; Dillner, Joakim; Roivainen, Merja; Bosi, Emanuele; Piemonti, Lorenzo

doi:10.1007/s00125-012-2591-4

Cited by 34 publications

(29 citation statements)

References 34 publications

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“…A recent report shows that a large proportion of type 1 diabetic patients have prolonged/persistent enterovirus infection associated with an inflammatory process in the gut mucosa, suggesting that the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes [8], [9]; however these findings have not been confirmed in another study [10].…”

Section: Introductionmentioning

confidence: 87%

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

et al. 2013

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Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients’sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients’ sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

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Section: Introductionmentioning

confidence: 87%

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

et al. 2013

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“…EV RNA-positive samples were more frequent among the cases than among the controls.Oikarinen et al, 2012 [98]EVLarge proportion of type 1 diabetes patients have prolonged/persistent EV infection associated with an inflammation process in gut mucosa.Mercalli et al, 2012 [99]EVSmall intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 controls and 27 individuals with coeliac disease analysed for the presence of EV RNA by in situ hybridisation and RT-PCR. Prolonged/persistent EV infections in gut mucosa are not common in patients with type 1 diabetes.Viskari et al, 2000 [100]EVThe rapid decrease in EV infection frequency in Finland may explain the increasing incidence of type 1 diabetes.Roivainen et al, 2002 [101]EVPatterns and consequences of EV infections investigated in cultured adult human isolated islets.…”

Section: How Can the Histopathological Hallmarks Of Diabetes Be Explamentioning

confidence: 99%

Potential viral pathogenic mechanism in human type 1 diabetes

Schneider

Herrath

2014

Diabetologia

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In type 1 diabetes, as a result of as yet unknown triggering events, auto-aggressive CD8+ T cells, together with a significant number of other inflammatory cells, including CD8+ T lymphocytes with unknown specificity, infiltrate the pancreas, leading to insulitis and destruction of the insulin-producing beta cells. Type 1 diabetes is a multifactorial disease caused by an interactive combination of genetic and environmental factors. Viruses are major environmental candidates with known potential effects on specific key points in the pathogenesis of type 1 diabetes and recent findings seem to confirm this presumption. However, we still lack well-grounded mechanistic explanations for how exactly viruses may influence type 1 diabetes aetiology. In this review we provide a summary of experimentally defined viral mechanisms potentially involved in the ontology of type 1 diabetes and discuss some novel hypotheses of how viruses may affect the initiation and natural history of the disease.

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“…Epidemiological studies have suggested that infections with enteroviruses, in particular those of the coxsackie B virus (CVB) serotypes, may be linked to islet autoimmunity and development of type 1 diabetes [1][2][3][4][5]. Other observations suggesting that infections with these viruses have a causative role in diabetes development come from studies that found enteroviruses more frequently in pancreases [6][7][8] and, in some studies, also gut biopsies [9][10][11], from patients with type 1 diabetes compared with healthy controls. Some enteroviruses, including the CVBs, are pancreatropic and can infect human beta cells in vitro, often with a detrimental outcome (e.g.…”

Section: Introductionmentioning

confidence: 99%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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No evidence of enteroviruses in the intestine of patients with type 1 diabetes

Cited by 34 publications

References 34 publications

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

Potential viral pathogenic mechanism in human type 1 diabetes

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

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