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Erschienen in: Diabetologia 3/2017

09.01.2017 | Article

Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity

verfasst von: Hanna Honkanen, Sami Oikarinen, Noora Nurminen, Olli H. Laitinen, Heini Huhtala, Jussi Lehtonen, Tanja Ruokoranta, Minna M. Hankaniemi, Valérie Lecouturier, Jeffrey W. Almond, Sisko Tauriainen, Olli Simell, Jorma Ilonen, Riitta Veijola, Hanna Viskari, Mikael Knip, Heikki Hyöty

Erschienen in: Diabetologia | Ausgabe 3/2017

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Abstract

Aims/hypothesis

This case–control study was nested in a prospective birth cohort to evaluate whether the presence of enteroviruses in stools was associated with the appearance of islet autoimmunity in the Type 1 Diabetes Prediction and Prevention study in Finland.

Methods

Altogether, 1673 longitudinal stool samples from 129 case children who turned positive for multiple islet autoantibodies and 3108 stool samples from 282 matched control children were screened for the presence of enterovirus RNA using RT-PCR. Viral genotype was detected by sequencing.

Results

Case children had more enterovirus infections than control children (0.8 vs 0.6 infections per child). Time-dependent analysis indicated that this excess of infections occurred more than 1 year before the first detection of islet autoantibodies (6.3 vs 2.1 infections per 10 follow-up years). No such difference was seen in infections occurring less than 1 year before islet autoantibody seroconversion or after seroconversion. The most frequent enterovirus types included coxsackievirus A4 (28% of genotyped viruses), coxsackievirus A2 (14%) and coxsackievirus A16 (11%).

Conclusions/interpretation

The results suggest that enterovirus infections diagnosed by detecting viral RNA in stools are associated with the development of islet autoimmunity with a time lag of several months.
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Literatur
2.
Zurück zum Zitat Yoon JW, Austin M, Onodera T, Notkins AL (1979) Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173–1179CrossRefPubMed Yoon JW, Austin M, Onodera T, Notkins AL (1979) Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173–1179CrossRefPubMed
3.
Zurück zum Zitat Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52:1143–1151CrossRefPubMed Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52:1143–1151CrossRefPubMed
4.
Zurück zum Zitat Yeung WC, Rawlinson WD, Craig ME (2011) Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ 342:d35CrossRefPubMedPubMedCentral Yeung WC, Rawlinson WD, Craig ME (2011) Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ 342:d35CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Hyoty H, Hiltunen M, Knip M et al (1995) A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes 44:652–657CrossRefPubMed Hyoty H, Hiltunen M, Knip M et al (1995) A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes 44:652–657CrossRefPubMed
7.
Zurück zum Zitat Helfand RF, Gary HE Jr, Freeman CY, Anderson LJ, Pallansch MA (1995) Serologic evidence of an association between enteroviruses and the onset of type 1 diabetes mellitus. Pittsburgh Diabetes Research Group. J Infect Dis 172:1206–1211CrossRefPubMed Helfand RF, Gary HE Jr, Freeman CY, Anderson LJ, Pallansch MA (1995) Serologic evidence of an association between enteroviruses and the onset of type 1 diabetes mellitus. Pittsburgh Diabetes Research Group. J Infect Dis 172:1206–1211CrossRefPubMed
8.
Zurück zum Zitat Green J, Casabonne D, Newton R (2004) Coxsackie B virus serology and type 1 diabetes mellitus: a systematic review of published case-control studies. Diabet Med 21:507–514CrossRefPubMed Green J, Casabonne D, Newton R (2004) Coxsackie B virus serology and type 1 diabetes mellitus: a systematic review of published case-control studies. Diabet Med 21:507–514CrossRefPubMed
9.
Zurück zum Zitat Oikarinen S, Martiskainen M, Tauriainen S et al (2011) Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes 60:276–279CrossRefPubMed Oikarinen S, Martiskainen M, Tauriainen S et al (2011) Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes 60:276–279CrossRefPubMed
10.
Zurück zum Zitat Oikarinen S, Tauriainen S, Hober D et al (2014) Virus antibody survey in different European populations indicates risk association between coxsackievirus B1 and type 1 diabetes. Diabetes 63:655–662CrossRefPubMed Oikarinen S, Tauriainen S, Hober D et al (2014) Virus antibody survey in different European populations indicates risk association between coxsackievirus B1 and type 1 diabetes. Diabetes 63:655–662CrossRefPubMed
11.
Zurück zum Zitat Laitinen OH, Honkanen H, Pakkanen O et al (2014) Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that portends type 1 diabetes. Diabetes 63:446–455CrossRefPubMed Laitinen OH, Honkanen H, Pakkanen O et al (2014) Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that portends type 1 diabetes. Diabetes 63:446–455CrossRefPubMed
12.
Zurück zum Zitat Cinek O, Stene LC, Kramna L et al (2014) 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. Diabetologia 57:2193–2200CrossRefPubMed Cinek O, Stene LC, Kramna L et al (2014) 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. Diabetologia 57:2193–2200CrossRefPubMed
13.
Zurück zum Zitat Simonen-Tikka ML, Pflueger M, Klemola P et al (2011) Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study. Diabetologia 54:2995–3002CrossRefPubMed Simonen-Tikka ML, Pflueger M, Klemola P et al (2011) Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study. Diabetologia 54:2995–3002CrossRefPubMed
14.
Zurück zum Zitat Tapia G, Cinek O, Rasmussen T et al (2011) Human enterovirus RNA in monthly fecal samples and islet autoimmunity in Norwegian children with high genetic risk for type 1 diabetes: the MIDIA study. Diabetes Care 34:151–155CrossRefPubMed Tapia G, Cinek O, Rasmussen T et al (2011) Human enterovirus RNA in monthly fecal samples and islet autoimmunity in Norwegian children with high genetic risk for type 1 diabetes: the MIDIA study. Diabetes Care 34:151–155CrossRefPubMed
15.
Zurück zum Zitat Graves PM, Rotbart HA, Nix WA et al (2003) Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes Autoimmunity Study in the Young (DAISY). Diabetes Res Clin Pract 59:51–61CrossRefPubMed Graves PM, Rotbart HA, Nix WA et al (2003) Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes Autoimmunity Study in the Young (DAISY). Diabetes Res Clin Pract 59:51–61CrossRefPubMed
16.
Zurück zum Zitat Stene LC, Oikarinen S, Hyoty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180CrossRefPubMedPubMedCentral Stene LC, Oikarinen S, Hyoty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Nanto-Salonen K, Kupila A, Simell S et al (2008) Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Lancet 372:1746–1755CrossRefPubMed Nanto-Salonen K, Kupila A, Simell S et al (2008) Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Lancet 372:1746–1755CrossRefPubMed
18.
Zurück zum Zitat Kukko M, Kimpimaki T, Korhonen S et al (2005) Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 90:2712–2717CrossRefPubMed Kukko M, Kimpimaki T, Korhonen S et al (2005) Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 90:2712–2717CrossRefPubMed
19.
Zurück zum Zitat Salminen KK, Vuorinen T, Oikarinen S et al (2004) Isolation of enterovirus strains from children with preclinical type 1 diabetes. Diabet Med 21:156–164CrossRefPubMed Salminen KK, Vuorinen T, Oikarinen S et al (2004) Isolation of enterovirus strains from children with preclinical type 1 diabetes. Diabet Med 21:156–164CrossRefPubMed
20.
Zurück zum Zitat Ilonen J, Kiviniemi M, Lempainen J et al (2016) Genetic susceptibility to type 1 diabetes in childhood - estimation of HLA class II associated disease risk and class II effect in various phases of islet autoimmunity. Pediatr Diabetes 17(Suppl 22):8–16CrossRefPubMed Ilonen J, Kiviniemi M, Lempainen J et al (2016) Genetic susceptibility to type 1 diabetes in childhood - estimation of HLA class II associated disease risk and class II effect in various phases of islet autoimmunity. Pediatr Diabetes 17(Suppl 22):8–16CrossRefPubMed
21.
Zurück zum Zitat Lonnrot M, Sjoroos M, Salminen K, Maaronen M, Hyypia T, Hyoty H (1999) Diagnosis of enterovirus and rhinovirus infections by RT-PCR and time-resolved fluorometry with lanthanide chelate labeled probes. J Med Virol 59:378–384CrossRefPubMed Lonnrot M, Sjoroos M, Salminen K, Maaronen M, Hyypia T, Hyoty H (1999) Diagnosis of enterovirus and rhinovirus infections by RT-PCR and time-resolved fluorometry with lanthanide chelate labeled probes. J Med Virol 59:378–384CrossRefPubMed
22.
Zurück zum Zitat Honkanen H, Oikarinen S, Pakkanen O et al (2013) Human enterovirus 71 strains in the background population and in hospital patients in Finland. J Clin Virol 56:348–353CrossRefPubMed Honkanen H, Oikarinen S, Pakkanen O et al (2013) Human enterovirus 71 strains in the background population and in hospital patients in Finland. J Clin Virol 56:348–353CrossRefPubMed
23.
Zurück zum Zitat Nix WA, Oberste MS, Pallansch MA (2006) Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J Clin Microbiol 44:2698–2704CrossRefPubMedPubMedCentral Nix WA, Oberste MS, Pallansch MA (2006) Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J Clin Microbiol 44:2698–2704CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Salminen K, Sadeharju K, Lonnrot M et al (2003) Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study. J Med Virol 69:91–98CrossRefPubMed Salminen K, Sadeharju K, Lonnrot M et al (2003) Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study. J Med Virol 69:91–98CrossRefPubMed
25.
Zurück zum Zitat Sadeharju K, Hamalainen AM, Knip M et al (2003) Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. Clin Exp Immunol 132:271–277CrossRefPubMedPubMedCentral Sadeharju K, Hamalainen AM, Knip M et al (2003) Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. Clin Exp Immunol 132:271–277CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Lempainen J, Tauriainen S, Vaarala O et al (2012) Interaction of enterovirus infection and cow’s milk-based formula nutrition in type 1 diabetes-associated autoimmunity. Diabetes Metab Res Rev 28:177–185CrossRefPubMed Lempainen J, Tauriainen S, Vaarala O et al (2012) Interaction of enterovirus infection and cow’s milk-based formula nutrition in type 1 diabetes-associated autoimmunity. Diabetes Metab Res Rev 28:177–185CrossRefPubMed
27.
Zurück zum Zitat Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed
28.
Zurück zum Zitat Jenson AB, Rosenberg HS, Notkins AL (1980) Pancreatic islet-cell damage in children with fatal viral infections. Lancet 2:354–358PubMed Jenson AB, Rosenberg HS, Notkins AL (1980) Pancreatic islet-cell damage in children with fatal viral infections. Lancet 2:354–358PubMed
29.
Zurück zum Zitat Chatterjee NK, Hou J, Dockstader P, Charbonneau T (1992) Coxsackievirus B4 infection alters thymic, splenic, and peripheral lymphocyte repertoire preceding onset of hyperglycemia in mice. J Med Virol 38:124–131CrossRefPubMed Chatterjee NK, Hou J, Dockstader P, Charbonneau T (1992) Coxsackievirus B4 infection alters thymic, splenic, and peripheral lymphocyte repertoire preceding onset of hyperglycemia in mice. J Med Virol 38:124–131CrossRefPubMed
30.
Zurück zum Zitat Simonen-Tikka ML, Hiekka AK, Klemola P et al (2012) Early human enterovirus infections in healthy Swedish children participating in the PRODIA pilot study. J Med Virol 84:923–930CrossRefPubMed Simonen-Tikka ML, Hiekka AK, Klemola P et al (2012) Early human enterovirus infections in healthy Swedish children participating in the PRODIA pilot study. J Med Virol 84:923–930CrossRefPubMed
31.
Zurück zum Zitat Tan CY, Ninove L, Gaudart J et al (2011) A retrospective overview of enterovirus infection diagnosis and molecular epidemiology in the public hospitals of Marseille, France (1985-2005). PLoS One 6:e18022CrossRefPubMedPubMedCentral Tan CY, Ninove L, Gaudart J et al (2011) A retrospective overview of enterovirus infection diagnosis and molecular epidemiology in the public hospitals of Marseille, France (1985-2005). PLoS One 6:e18022CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat van der Sanden SM, Koopmans MP, van der Avoort HG (2013) Detection of human enteroviruses and parechoviruses as part of the national enterovirus surveillance in the Netherlands, 1996-2011. Eur J Clin Microbiol Infect Dis 32:1525–1531CrossRefPubMed van der Sanden SM, Koopmans MP, van der Avoort HG (2013) Detection of human enteroviruses and parechoviruses as part of the national enterovirus surveillance in the Netherlands, 1996-2011. Eur J Clin Microbiol Infect Dis 32:1525–1531CrossRefPubMed
33.
Zurück zum Zitat Champsaur H, Dussaix E, Samolyk D, Fabre M, Bach C, Assan R (1980) Diabetes and Coxsackie virus B5 infection. Lancet 1:251CrossRefPubMed Champsaur H, Dussaix E, Samolyk D, Fabre M, Bach C, Assan R (1980) Diabetes and Coxsackie virus B5 infection. Lancet 1:251CrossRefPubMed
34.
Zurück zum Zitat Wagenknecht LE, Roseman JM, Herman WH (1991) Increased incidence of insulin-dependent diabetes mellitus following an epidemic of Coxsackievirus B5. Am J Epidemiol 133:1024–1031PubMed Wagenknecht LE, Roseman JM, Herman WH (1991) Increased incidence of insulin-dependent diabetes mellitus following an epidemic of Coxsackievirus B5. Am J Epidemiol 133:1024–1031PubMed
35.
Zurück zum Zitat Clements GB, Galbraith DN, Taylor KW (1995) Coxsackie B virus infection and onset of childhood diabetes. Lancet 346:221–223CrossRefPubMed Clements GB, Galbraith DN, Taylor KW (1995) Coxsackie B virus infection and onset of childhood diabetes. Lancet 346:221–223CrossRefPubMed
36.
Zurück zum Zitat Andreoletti L, Hober D, Hober-Vandenberghe C et al (1997) Detection of coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus. J Med Virol 52:121–127CrossRefPubMed Andreoletti L, Hober D, Hober-Vandenberghe C et al (1997) Detection of coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus. J Med Virol 52:121–127CrossRefPubMed
37.
Zurück zum Zitat Roivainen M, Knip M, Hyoty H et al (1998) Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78CrossRefPubMed Roivainen M, Knip M, Hyoty H et al (1998) Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78CrossRefPubMed
38.
Zurück zum Zitat Chehadeh W, Kerr-Conte J, Pattou F et al (2000) Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol 74:10153–10164CrossRefPubMedPubMedCentral Chehadeh W, Kerr-Conte J, Pattou F et al (2000) Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol 74:10153–10164CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Yin H, Berg AK, Westman J, Hellerstrom C, Frisk G (2002) Complete nucleotide sequence of a Coxsackievirus B-4 strain capable of establishing persistent infection in human pancreatic islet cells: effects on insulin release, proinsulin synthesis, and cell morphology. J Med Virol 68:544–557CrossRefPubMed Yin H, Berg AK, Westman J, Hellerstrom C, Frisk G (2002) Complete nucleotide sequence of a Coxsackievirus B-4 strain capable of establishing persistent infection in human pancreatic islet cells: effects on insulin release, proinsulin synthesis, and cell morphology. J Med Virol 68:544–557CrossRefPubMed
40.
Zurück zum Zitat Dotta F, Censini S, van Halteren AG et al (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 104:5115–5120CrossRefPubMedPubMedCentral Dotta F, Censini S, van Halteren AG et al (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 104:5115–5120CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA, Centers for Disease Control and Prevention (2006) Enterovirus surveillance--United States, 1970-2005. MMWR Surveill Summ 55:1–20PubMed Khetsuriani N, Lamonte-Fowlkes A, Oberst S, Pallansch MA, Centers for Disease Control and Prevention (2006) Enterovirus surveillance--United States, 1970-2005. MMWR Surveill Summ 55:1–20PubMed
42.
Zurück zum Zitat Fujimoto T, Shinohara M, Ito M et al (2007) Detection of dual-infected cases of adenoviruses and coxsackieviruses type B by real-time PCR but not by the conventional viral culture technique. Clin Lab 53:605–609PubMed Fujimoto T, Shinohara M, Ito M et al (2007) Detection of dual-infected cases of adenoviruses and coxsackieviruses type B by real-time PCR but not by the conventional viral culture technique. Clin Lab 53:605–609PubMed
43.
Zurück zum Zitat Lu QB, Wo Y, Wang HY et al (2014) Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China. J Med Microbiol 63:408–414CrossRefPubMed Lu QB, Wo Y, Wang HY et al (2014) Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China. J Med Microbiol 63:408–414CrossRefPubMed
44.
Zurück zum Zitat Sadeharju K, Knip M, Hiltunen M, Akerblom HK, Hyoty H (2003) The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens. Diabetologia 46:1100–1105CrossRefPubMed Sadeharju K, Knip M, Hiltunen M, Akerblom HK, Hyoty H (2003) The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens. Diabetologia 46:1100–1105CrossRefPubMed
45.
Zurück zum Zitat Witso E, Tapia G, Cinek O, Pociot FM, Stene LC, Ronningen KS (2011) Polymorphisms in the innate immune IFIH1 gene, frequency of enterovirus in monthly fecal samples during infancy, and islet autoimmunity. PLoS One 6:e27781CrossRefPubMedPubMedCentral Witso E, Tapia G, Cinek O, Pociot FM, Stene LC, Ronningen KS (2011) Polymorphisms in the innate immune IFIH1 gene, frequency of enterovirus in monthly fecal samples during infancy, and islet autoimmunity. PLoS One 6:e27781CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Witso E, Cinek O, Tapia G, Rasmussen T, Stene LC, Ronningen KS (2012) HLA-DRB1-DQA1-DQB1 genotype and frequency of enterovirus in longitudinal monthly fecal samples from healthy infants. Viral Immunol 25:187–192PubMed Witso E, Cinek O, Tapia G, Rasmussen T, Stene LC, Ronningen KS (2012) HLA-DRB1-DQA1-DQB1 genotype and frequency of enterovirus in longitudinal monthly fecal samples from healthy infants. Viral Immunol 25:187–192PubMed
47.
Zurück zum Zitat Witso E, Cinek O, Tapia G et al (2015) Genetic determinants of enterovirus infections: polymorphisms in type 1 diabetes and innate immune genes in the MIDIA study. Viral Immunol 28:556–563CrossRefPubMed Witso E, Cinek O, Tapia G et al (2015) Genetic determinants of enterovirus infections: polymorphisms in type 1 diabetes and innate immune genes in the MIDIA study. Viral Immunol 28:556–563CrossRefPubMed
Metadaten
Titel
Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity
verfasst von
Hanna Honkanen
Sami Oikarinen
Noora Nurminen
Olli H. Laitinen
Heini Huhtala
Jussi Lehtonen
Tanja Ruokoranta
Minna M. Hankaniemi
Valérie Lecouturier
Jeffrey W. Almond
Sisko Tauriainen
Olli Simell
Jorma Ilonen
Riitta Veijola
Hanna Viskari
Mikael Knip
Heikki Hyöty
Publikationsdatum
09.01.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 3/2017
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4177-z

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