Enterovirus RNA in Blood Is Linked to the Development of Type 1 Diabetes

Abstract

OBJECTIVETo assess whether the detection of enterovirus RNA in blood predicts the development of clinical type 1 diabetes in a prospective birth cohort study. Further, to study the role of enteroviruses in both the initiation of the process and the progression to type 1 diabetes.RESEARCH DESIGN AND METHODSThis was a nested case-control study where all case children (N = 38) have progressed to clinical type 1 diabetes. Nondiabetic control children (N = 140) were pairwise matched for sex, date of birth, hospital district, and HLA-DQ–conferred genetic susceptibility to type 1 diabetes. Serum samples, drawn at 3- to 12-month intervals, were screened for enterovirus RNA using RT-PCR.RESULTSEnterovirus RNA–positive samples were more frequent among the case subjects than among the control subjects. A total of 5.1% of the samples (17 of 333) in the case group were enterovirus RNA–positive compared with 1.9% of the samples (19 of 993) in the control group (P < 0.01). The strongest risk for type 1 diabetes was related to enterovirus RNA positivity during the 6-month period preceding the first autoantibody-positive sample (odds ratio 7.7 [95% CI 1.9–31.5]). This risk effect was stronger in boys than in girls.CONCLUSIONSThe present study supports the hypothesis that enteroviruses play a role in the pathogenesis of type 1 diabetes, especially in the initiation of the β-cell damaging process. The enterovirus-associated risk for type 1 diabetes may be stronger in boys than in girls.

Is Type 1 Diabetes “Going Viral”?

“…The studies by Ferreira et al (4) and Kallionpää et al (5) are the first to demonstrate activation of the innate IFN pathway prior to initiation of islet autoimmunity, and they support previous studies demonstrating an increased frequency of infections prior to development of autoantibodies (18,19). Together, they argue that against the backdrop of a genetic predisposition to autoimmunity viral infections can, in some individuals, be causal in development of T1D.…”

Innate Immune Activity Is Detected Prior to Seroconversion in Children With HLA-Conferred Type 1 Diabetes Susceptibility

“…IFN-a and -b were not differentially regulated in our data, indicating that the blood cells are showing an indirect response to cytokines produced elsewhere. For instance, enteroviral infections have been detected in the b-cells of newly diagnosed patients (36), and signs of infections have been observed a few months prior to seroconversion to autoantibody positivity (37) and during the 6-month period preceding seroconversion (3,4). Moreover, the accompanying study (34) demonstrates an association between upper respiratory tract infections and upregulation of IFN-responsive genes.…”

“…When combined with a susceptible genetic background, largely unknown random environmental factors probably contribute to the breakdown of self-tolerance. For instance, dietary factors, such as early exposure to foreign complex proteins (2) and vitamin D deficiency, have been associated with development of T1D, and viral infections are believed to trigger autoimmunity (3,4). Prevalence of T1D is also associated with Westernized lifestyle and level of hygiene (5).…”

Case report: type 1 diabetes in monozygotic quadruplets

“…We focused on enteroviruses and coxsackie viruses as they are suspected to have a role in T1D development. [13][14][15] Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms using Aneufast multiplex QF-PCR kit (molGENTIX, S.L., Barcelona, Spain), recommended by CODIS (Combined DNA Index System). 20 …”

“…[9][10][11][12] Notably, and in this context, several recently published findings suggest a strong link between T1D and enteroviral infections. [13][14][15] To prevent the clinical onset of T1D, immuno-intervention should be undertaken in the clinically silent pre-diabetic phase. However, it is difficult to identify suitable candidates for such interventions.…”