Enterovirus infections with β‐cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies

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Abstract
Enterovirus infections have been associated with type 1 diabetes in a number of reports. Recent prospective studies have suggested that enterovirus infections initiate the autoimmune process. Variation in virulence and replication pattern between strains of a serotype has also been shown. The aim was to study if there were specific Coxsackievirus strains that were associated more often with the type 1 diabetes children than with controls and/or siblings and to analyse if there was any time-relationship between such infections and the appearance of antibodies against glutamic acid decarboxylase 65 (GAD65). In the present study, serum was tested from newly diagnosed type 1 diabetes children, their siblings and matched controls for neutralising antibodies against different strains of Coxsackievirus B (CBV). Tests for the presence of antibodies against GAD65 in the same groups were also carried out. Newly diagnosed type 1 diabetes children revealed higher titres of neutralising antibodies against a strain of Coxsackievirus B4 (CBV-4, VD2921) that has been shown to cause persistent infection in human pancreatic islet cells. The type 1 diabetes child and its sibling often encountered the same infection. Among the former, 16 of 27 (59%) had a significant rise in neutralising antibodies. Eight of the type 1 diabetes children had such a rise against a recombinant strain, V89 4557. Among the siblings 10 of 13 (77%) had significant titre increases. Among the type 1 diabetes children, increasing neutralising titres was associated positively with increasing antibody levels against GAD65. All siblings with antibodies against GAD 65 had significant titre increase against any of the CBV strains. J. Med. Virol. 73:450–459, 2004.

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