Antibodies against Coxsackievirus B4 in Sardinian schoolchildren with positivity to islet cell antibodies

— Background: Infections caused by enteroviruses, particularly Coxsackievirus B4 (CVB4), have been suggested to be diabetogenic in genetically predisposed subjects. The onset of autoimmune processes leading to Type 1 Diabetes Mellitus (T1DM) may precede clinical diagnosis by years, and it is unknown at what stage viral infection might be significant. The Sardinian Island has the second highest incidence of T1DM in the world, close to Finland. To date, no studies have been performed to evaluate a possible role of CBV4 infection on T1DM development in Sardinian population. In our study, we evaluated the possible relationship between CBV4 infection and pre-diabetic (Islet Cell Antibodies, ICA-positivity) status in Sardinian schoolchildren. The relationships between CBV4 infection and the appearance of other diabetes-related autoantibodies, namely glutamic acid decarboxylase antibodies (GADA), and protein tyrosine phosphatase-2 antibodies (IA2-A), whose positivity dramatically increases the PPV for T1DM development, were also studied. — Patients and Methods: 69 ICA-positive schoolchildren and 69 ICA-negative controls were studied. ICA were measured by conventional indirect immunofluorescence, and antibodies against CVB4 (CBV4-Ab) were measured by microneutralization test. GADA and IA2-A were measured by radioimmunoprecipitation on the sera of 121 out of the 138 subjects of the study. — Results: The number of schoolchildren which showed positivity to any titer of CBV4-Ab was 44 in the ICA-positive group (63.8%), and 51 (73.9%) in the ICA-negative group (p = NS). The CBV4-Ab frequency in GADApositive and GADA-negative subjects, and in IA2-A-positive and IA2-A-negative subjects was not different. — Conclusions: Our study, in Sardinian schoolchildren, does not support a role of CBV4 infection in the appearance of pancreatic islet autoimmunity.