The viral paradigm in type 1 diabetes: Who are the main suspects?

Rodríguez-Calvo, Teresa; Sabouri, Somayeh; Anquetil, Florence; Herrath, Matthias G. von

doi:10.1016/j.autrev.2016.07.019

Cited by 59 publications

(47 citation statements)

References 71 publications

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“…Studies in mice clearly document that virus infection can trigger damage to the islets (13)(14)(15)(16). Furthermore, intestinal eukaryotic viruses have been implicated in triggering human T1D, based mostly on seroepidemiologic studies of responses to one or a few candidate viruses (17)(18)(19). However, in another study, no changes in the virome were detected for 3-9 mo before the development of autoimmunity (20).…”

mentioning

confidence: 99%

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Zhao

Vatanen

Droit

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

250

240

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Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment ofCircoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.

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mentioning

confidence: 99%

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Zhao

Vatanen

Droit

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

250

240

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“…Respiratory infections in early life and type 1 diabetes have been linked [4–8], and we can consider influenza-like illness as a respiratory viral infection caused by influenza or other viruses. These, and other common viruses causing infection with fever, could be important as cytokine inducer and T cell activators [3]. Our finding that pandemic influenza diagnosis in specialist healthcare was more strongly associated with type 1 diabetes may possibly indicate that an association with type 1 diabetes is stronger with severe infections (needing hospitalisation or other type of specialist care).…”

Section: Discussionmentioning

confidence: 88%

“…Viruses may influence susceptibility and trigger autoimmunity in individuals genetically predisposed to diabetes [1, 2]. Enteroviruses and other viruses have been most frequently studied in relation to type 1 diabetes [3]. Recently, respiratory virus infections have also been associated with the development of islet autoimmunity and the first manifestations of clinical symptoms of type 1 diabetes [4–8].…”

Section: Introductionmentioning

confidence: 99%

Pandemic influenza and subsequent risk of type 1 diabetes: a nationwide cohort study

et al. 2018

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Aims/hypothesisCase reports have linked influenza infections to the development of type 1 diabetes. We investigated whether pandemic and seasonal influenza infections were associated with subsequent increased risk of type 1 diabetes.MethodsIn this population-based registry study, we linked individual-level data from national health registries for the entire Norwegian population under the age of 30 years for the years 2006–2014 (2.5 million individuals). Data were obtained from the National Registry (population data), the Norwegian Patient Registry (data on inpatient and outpatient specialist care), the Primary Care Database, the Norwegian Prescription Database and the Norwegian Surveillance System for Communicable Diseases. Pandemic influenza was defined as either a clinical influenza diagnosis during the main pandemic period or a laboratory-confirmed test. Seasonal influenza was defined by a clinical diagnosis of influenza between 2006 and 2014. We used Cox regression to estimate HRs for new-onset type 1 diabetes after an influenza infection, adjusted for year of birth, sex, place of birth and education.ResultsThe adjusted HR for type 1 diabetes after pandemic influenza infection was 1.19 (95% CI 0.97, 1.46). In the subgroup with laboratory-confirmed influenza A (H1N1), influenza was associated with a twofold higher risk of subsequent type 1 diabetes before age 30 years (adjusted HR: 2.26, 95% CI 1.51, 3.38).Conclusions/interpretationOverall, we could not demonstrate a clear association between clinically reported pandemic influenza infection and incident type 1 diabetes. However, we found a twofold excess of incident diabetes in the subgroup with laboratory-confirmed pandemic influenza A (H1N1).Electronic supplementary materialThe online version of this article (10.1007/s00125-018-4662-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…This is evident from the fact that not all individuals who carry the genetic risk factors develop CD. Similarly, viruses such as enteroviruses and herpesviruses [42] have also been described as the triggering factors for T1DM [43]. Since in most of the cases, T1DM manifests first followed by CD, so here we will try to elucidate the cascade of events in APS-4 subtype in this manner and is shown in Figure 2.…”

Section: Pathophysiologymentioning

confidence: 99%

Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment

Kaur

Bhadada

Minz

et al. 2018

Dig Dis

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Background: A complex interplay between genetic and environmental factors contributes to disease etiology of most of the autoimmune disorders. Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are polygenic autoimmune diseases that have high propensity to coexist due to shared etiological factors like genetics and clinico-pathological overlaps. Summary: The mean prevalence rate for coexistence of these diseases is 8%, and this value is a gross underestimation as reported from biopsy-proven symptomatic cases. The prevalence rate will rise when studies will excavate bottom layers of the “celiac iceberg” to detect potential and silent celiac cases. The concomitant presence of both these disorders is a complex situation immunologically as well as clinically. There is an accentuated breakdown of tolerance and proinflammatory cytokine storm that leads to the progression of organ-specific autoimmunity to systemic. No immunomodulating drugs are advocated as exogenous insulin supplementation and gluten exclusion are recommended for T1DM and CD respectively. Nevertheless, these pose certain challenges to both the clinicians and the patients, as gluten free diet (GFD) has been described to have an impact on glycemic control, bone health, and vascular complications. Also intermittent gluten intake by these patients due to non-compliance with GFD also stimulates the autoreactive immune cells that result in an augmented immune response. Key Messages: Large public health studies are needed to estimate the prevalence of all forms of CD in T1DM patients. Strict global guidelines need to be formulated for the disease management and prognosis, and there is also a need for an extensive research on each front to thoroughly understand the co-occurrence of these diseases.

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The viral paradigm in type 1 diabetes: Who are the main suspects?

Cited by 59 publications

References 71 publications

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Pandemic influenza and subsequent risk of type 1 diabetes: a nationwide cohort study

Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment

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