Читать книгу Clinical Dilemmas in Diabetes - Группа авторов - Страница 38

Certain viral infections may play a role in the pathogenesis of human T1D. Congenital rubella is the classical example of virus‐induced diabetes in human beings, but effective immunization programs have eliminated congenital rubella in most Western countries. Currently, the main candidate for a viral trigger of human diabetes is members of the group of Enterovirus [14]. They are small non‐enveloped RNA viruses, which belong to the Picornavirus family. They consist of more than 60 different serotypes, with the Polioviruses being their best‐known representatives. Enterovirus infections are frequent among children and adolescents causing aseptic meningitis, myocarditis, rash, hand‐food‐and‐mouth disease, paralysis, respiratory infections, and severe systemic infections in newborn infants. Most infections, however, are subclinical or manifest with mild respiratory symptoms. The primary replication of the virus occurs in the lymphoid tissues of the pharynx and small intestine, and during the following viremic phase the virus can spread to various organs including the β‐cells.

Theoretically, Enterovirus could cause β‐cell damage by two main mechanisms. They may infect β‐cells and destroy them directly or they may induce an autoimmune response against β‐cells. Direct virus‐induced damage has been supported by studies showing that Enterovirus are present in β‐cells in patients who have died from severe systemic Enterovirus infection and that the islet‐cells of these patients are damaged. Enterovirus can also infect and damage β‐cells in vitro and induce the expression of interferon‐alpha and HLA‐class I molecules in β‐cells thus mimicking the situation observed in the pancreas of patients affected by T1D. The first reports connecting Enterovirus infections to T1D were published more than 30 years ago, showing that the seasonal variation in the onset of T1D follows that of Enterovirus infections. At the same time antibodies against Coxsackievirus B serotypes were found to be more frequent in patients with newly diagnosed T1D than in control subjects [14]. Enterovirus have also been isolated from patients with newly diagnosed T1D. In one case report Coxsackievirus B4 was isolated from the pancreas of a child who had died from diabetic ketoacidosis, and this virus caused diabetes when transferred to a susceptible mouse strain. The β‐cells of diabetic patients also express interferon‐alpha, a cytokine that is induced during viral infections, suggesting the presence of some virus in the β‐cells. Prospective studies are particularly valuable in the evaluation of viral triggers because they cover all stages of the β‐cell damaging process.

Enterovirus are not the only viruses that have been connected to the pathogenesis of T1D. Mumps, measles, cytomegalovirus, and retroviruses also have been found to be associated with T1D, but the evidence is less convincing than that for Enterovirus.