{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:22:58Z","timestamp":1791238978949,"version":"4.1.0"},"reference-count":94,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,3,2]],"date-time":"2012-03-02T00:00:00Z","timestamp":1330646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES<\/jats:p>\n               <jats:p>Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.<\/jats:p>\n               <jats:p>The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and\/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2011.04555.x","type":"journal-article","created":{"date-parts":[[2011,12,28]],"date-time":"2011-12-28T21:55:51Z","timestamp":1325109351000},"page":"12-23","source":"Crossref","is-referenced-by-count":80,"title":["Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies"],"prefix":"10.1093","volume":"168","author":[{"given":"L C","family":"Stene","sequence":"first","affiliation":[{"name":"Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Rewers","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,3,2]]},"reference":[{"key":"2021122708380493100_b1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/9780470779750.ch24","volume-title":"The epidemiology of diabetes mellitus","author":"Stene","year":"2008"},{"key":"2021122708380493100_b2","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1136\/bmj.3.5671.627","article-title":"Viral antibodies in diabetes mellitus","volume":"3","author":"Gamble","year":"1969","journal-title":"BMJ"},{"key":"2021122708380493100_b3","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1056\/NEJM197905243002102","article-title":"Isolation of a virus from the pancreas of a child with diabetic ketoacidosis","volume":"300","author":"Yoon","year":"1979","journal-title":"N Engl J Med"},{"key":"2021122708380493100_b4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0140-6736(01)05415-0","article-title":"Type 1 diabetes: new perspectives on disease pathogenesis and treatment","volume":"358","author":"Atkinson","year":"2001","journal-title":"Lancet"},{"key":"2021122708380493100_b5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1507\/endocrj.K09E-291","article-title":"Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes","volume":"57","author":"Shibasaki","year":"2010","journal-title":"Endocr J"},{"key":"2021122708380493100_b6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1365-2249.2011.04554.x","article-title":"Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma","volume":"168","author":"Coppieters","year":"2012","journal-title":"Clin Exp Immunol"},{"key":"2021122708380493100_b7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1365-2249.2011.04557.x","article-title":"Immunology in the clinic review series; focus on type 1 diabetes and viruses: the innate immune response to enteroviruses and its possible role in regulating type 1 diabetes","volume":"168","author":"Lind","year":"2012","journal-title":"Clin Exp Immunol"},{"key":"2021122708380493100_b8","doi-asserted-by":"crossref","first-page":"708","DOI":"10.2337\/diabetes.49.5.708","article-title":"Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets","volume":"49","author":"Serreze","year":"2000","journal-title":"Diabetes"},{"key":"2021122708380493100_b9","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/jaut.2000.0486","article-title":"Requirements for viral-mediated autoimmune diabetes: \u03b2-cell damage and immune infiltration","volume":"16","author":"Horwitz","year":"2001","journal-title":"J Autoimmun"},{"key":"2021122708380493100_b10","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1172\/JCI200422557","article-title":"A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes","volume":"114","author":"Christen","year":"2004","journal-title":"J Clin Invest"},{"key":"2021122708380493100_b11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.virol.2004.06.049","article-title":"Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: insulitis determines susceptibility of pancreatic islets to virus infection","volume":"329","author":"Drescher","year":"2004","journal-title":"Virology"},{"key":"2021122708380493100_b12","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.2337\/db10-0866","article-title":"Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY)","volume":"59","author":"Stene","year":"2010","journal-title":"Diabetes"},{"key":"2021122708380493100_b13","first-page":"161","article-title":"The role of viruses in the pathogenesis of pancreatic disease and diabetes mellitus","volume":"19","author":"Craighead","year":"1975","journal-title":"Prog Med Virol"},{"key":"2021122708380493100_b14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/oxfordjournals.epirev.a036226","article-title":"The epidemiology of insulin dependent diabetes, with particular reference to the relationship of virus infection to its etiology","volume":"2","author":"Gamble","year":"1980","journal-title":"Epidemiol Rev"},{"key":"2021122708380493100_b15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/dmrr.337","article-title":"A new look at viruses in type 1 diabetes","volume":"19","author":"Jun","year":"2003","journal-title":"Diabetes Metab Res 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Observations on viral excretion, seroimmunity, intrafamilial spread and illness association in coxsackie and echovirus infections","volume":"89","author":"Kogon","year":"1969","journal-title":"Am J Epidemiol"},{"key":"2021122708380493100_b26","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1128\/JCM.00653-06","article-title":"Natural circulation of human enteroviruses: high prevalence of human enterovirus A infections","volume":"44","author":"Wits\u00f8","year":"2006","journal-title":"J Clin Microbiol"},{"key":"2021122708380493100_b27","first-page":"33","article-title":"Comparative genomics of the coxsackie B viruses and related enteroviruses","volume":"323","author":"Oberste","year":"2008","journal-title":"Curr Top Microbiol Immunol"},{"key":"2021122708380493100_b28","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1464-5491.2004.01097.x","article-title":"Isolation of enterovirus strains from children with preclinical Type 1 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