Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetes

Abstract

Ljungan virus (LV), a Parechovirus of the Picornavirus family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87-012 LV isolate. The goal was to determine NLVA titres in incident 0-18 years old newly diagnosed type 1 diabetes patients (n=67) and school children controls (n=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (P=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (P=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.

Keywords: Ljungan Virus; Type 1 diabetes; beta cell autoimmunity; glutamic acid decarboxylase autoantibodies; human pathogen; neutralization assay.

Fig. 1.

Distributions of the log-transformed neutralizing Ljungan virus antibodies (NLVA) binding levels among type 1 diabetes cases (n=67) and controls (n=292). (a) Shows the quantiles of each of these distributions compared to the quantiles of the Normal (0, 1) distribution (red triangles for T1D cases, blue circles for controls). (b) Shows the cumulative distribution for T1D cases (red dashed line) and controls (blue solid line). There are many ties due to the lower and upper detection limits, but there is evidence that the distributions are different between T1D cases and controls (p-value=0.017).