Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case‐control studies

Green, J; Casabonne, Delphine; Newton, Rob

doi:10.1111/j.1464-5491.2004.01182.x

Cited by 94 publications

(58 citation statements)

References 50 publications

(75 reference statements)

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“…The lack of this information could also explain the variable results from previous studies that have been based on assays detecting several different enterovirus types as a group (2,12). Despite the importance of this topic, large-scale systematic studies aimed at identifying diabetogenic enterovirus serotypes have not been performed.…”

mentioning

confidence: 56%

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Laitinen¹,

Honkanen

Pakkanen³

et al. 2014

Diabetes

229

221

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The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.

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mentioning

confidence: 56%

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Laitinen¹,

Honkanen

Pakkanen³

et al. 2014

Diabetes

229

221

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“…Serological studies and studies detecting viruses in respiratory or stool samples detect exposure, but not invasion (Figure 2). In fact, this seems to be the case, since serological studies and the detection of EVs from stool samples have indicated only weak or no risk effect [21][22][23]. In contrast, studies based on virus detection from blood or pancreas have shown a risk effect [24,25].…”

Section: Role Of Non-inva-sive and Invasive Infectionmentioning

confidence: 90%

“…According to published meta-analyses, the association between EV and T1D is quite strong in studies which have been based on direct virus detection from blood or tissues (odds ratios ranging from 4 to 10) [24]. However, serological studies have shown more variable results [21], possibly because they measure the general exposure and not invasive infection. The discovery of IFIH1 as a risk gene for T1D has recently offered a feasible mechanistic explanation for this association [32,34].…”

Section: How To Prove Causality?mentioning

confidence: 99%

Virus Infections as Potential Targets of Preventive Treatments for Type 1 Diabetes

Nurminen

Oikarinen²,

Hyöty

2012

Rev Diabet Stud

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Environmental factors play an important role in the pathogenesis of type 1 diabetes, and are attractive targets for preventive interventions. Several studies have shown that viruses can cause diabetes in animals, indicating their potential as candidates for environmental triggering agents. However, human studies have been hampered by the complex nature of the disease pathogenesis, leaving the question of viral etiology unanswered. Significant progress has recently been made in this field by searching for viruses within pancreatic tissue samples, and by carrying out prospective studies. Consequently, there is increasing evidence for a group of enteroviruses acting as possible environmental key triggers. In past studies, these viruses have been linked to type 1 diabetes. Recent studies have shown that they exert tropism to pancreatic islets, and that they are associated with the start of the beta-cell damaging process. Also, polymorphisms of the gene coding for the innate immune system sensor for enteroviruses (IFIH1) were found to modulate the risk of diabetes. Based on these findings, interest in the possible development of vaccines against these viruses has increased. However, even if enterovirus vaccines (polio vaccines) are effective and safe, we currently lack necessary information for the development of a vaccine against diabetogenic enteroviruses, e.g. regarding the identification of their specific serotypes and the causal relationship between these viruses and diabetes initiation. Ongoing research projects are currently addressing these questions, and will hopefully increase the consensus in this field. Also, new sequencing technologies will provide additional information about the whole virome, which could enable the discovery of new candidate viruses.

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“…Rubella virus (Karvonen et al, 1993), mumps virus (Hyoty et al, 1988, cytomegalovirus (Ward et a., 1979), rotavirus (Honeyman et al, 2000) and enteroviruses (EV) (Lonnrot et al, 2000;Stene et al, 2010) have all been suggested as environmental factors contributing to type 1 diabetes. EV, especially those of the Coxsackievirus B (CVB) group (Hyöty et al, 1988;Varela-Calvino & Peakman , 2003;Green et al, 2004), are historically the prime suspects as important aetiological determinants and seroepidemiological, histopathological, animal studies, and in vitro experiments have provided the strongest overall evidence for these viruses. The EV genus of the Picornaviridae family is a large group of human pathogens traditionally divided into polioviruses, coxsackieviruses, echoviruses and the new EV, and each group contains a range of serotypes (King et al, 2000;Roivainen, 2006).…”

Section: Enteroviruses and Type 1 Diabetesmentioning

confidence: 99%

Islet Endothelium: Role in Type 1 Diabetes and in Coxsackievirus Infections

Favaro¹,

Miceli²,

Camussi³

et al. 2011

Type 1 Diabetes Complications

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Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case‐control studies

Abstract: The results of these studies are inconsistent and do not provide convincing evidence for or against an association between Coxsackie B virus infection and Type 1 diabetes mellitus. Better designed studies using effective assays are needed to resolve this important issue.

Cited by 94 publications

References 50 publications

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Virus Infections as Potential Targets of Preventive Treatments for Type 1 Diabetes

Islet Endothelium: Role in Type 1 Diabetes and in Coxsackievirus Infections

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