Detection of Enterovirus RNA in Peripheral Blood Mononuclear Cells of Type 1 Diabetic Patients Beyond the Stage of Acute Infection

Abstract

Previous studies have shown that enteroviral RNA can be detected in blood at the onset of type 1 diabetes (T1D). The infection may play a role in triggering T1D and genetic host factors may contribute to this process. We investigated (1) whether enterovirus is present at the onset of T1D in peripheral blood mononuclear cells (PBMC), plasma, throat, or stool, and (2) whether enteroviral presence is linked with HLA-DR type and/or polymorphisms in melanoma differentiation-associated gene 5 (MDA5) and 2'-5' oligoadenylate synthetase 1 (OAS1), factors of antiviral immunity. To this end, PBMC, plasma, throat, and stool samples from 10 T1D patients and 20 unrelated controls were tested for the presence of enteroviruses (RT-PCR), for HLA-DR type, and polymorphisms in MDA5 and OAS1. Enterovirus RNA was detected in PBMC of 4/10 T1D patients, but none of 20 controls. Plasma was positive in 2/10 T1D patients and none of 20 controls, suggesting that enteroviruses found at the onset of T1D are mainly present in PBMC. All throat samples from positive T1D patients were virus-negative and only 1 fecal sample was positive. The negative results for all throat and most stool samples argues against acute infection. Enterovirus presence was linked with HLA-DR4, but not with polymorphisms in MDA5 or OAS1.

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

“…Our source of RNA (i.e. packed blood cells) may bear a certain 'memory' of past viral infections because peripheral white blood cells are permissive to enterovirus infection [16] and may be a better source of enterovirus RNA than plasma or serum [17,18]. Thus, we speculate that the enterovirus positivity we observed may reflect infection occurring over longer periods of time, leaving the direction of the causality unresolved.…”

Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III

“…Including the present study, we gathered seven publications with data on the rs7574865 SNP (Lee et al, 2008;Martínez et al, 2008a;Zervou et al, 2008;Howson et al, 2011;Park et al, 2011;Bi et al, 2013) and ten for the rs1990760 SNP (Smyth et al, 2006(Smyth et al, , 2008Martínez et al, 2008b;Aminkeng et al, 2009;Jermendy et al, 2009;Liu et al, 2009;Schulte et al, 2010;Yang et al, 2012;Bouças et al, 2013;Zurawek et al, 2015). The total number of cases and controls was 1392 and 1629 for the rs7574865 SNP and 25,092 and 28,544 for the rs1990760 SNP, respectively.…”

Echovirus Epidemics, Autoimmunity, and Type 1 Diabetes

“…The frequency of HEV genome positivity appeared to vary according to the specimen (Schulte et al, 2010a). In newly diagnosed T1D patients, the highest frequency of HEV RNA is detected in peripheral blood mononuclear cells (PBMC) followed by plasma or serum.…”

“…This finding suggests that an asymptomatic/low level infection takes place in children during the initial stages of the disease. In this regard, it should be pointed out that the amount of HEV genomes in serum/plasma and blood cells is extremely low and can only be evidence with highly sensitive methods (Sarmiento et al, 2007a;Schulte et al, 2010a). These findings indicate that small amounts of HEVs may derive from infected cells, e.g., cells of the islets of Langerhans islets or cell-debris (Schulte et al, 2010a;Schulte et al, 2010b).…”