nach oben

Current Diabetes Reports

Erschienen in:

01.11.2018 | Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors)

Enteroviral Infections as a Trigger for Type 1 Diabetes

verfasst von: Teresa Rodriguez-Calvo

Erschienen in: Current Diabetes Reports | Ausgabe 11/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

To provide an overview of studies that have detected enteroviruses (EV) in samples from people with type 1 diabetes (T1D), the techniques they have used, and which challenges they have encountered.

Recent Findings

Recent studies have detected EVs in serum, blood, stools, nasal swabs, and pancreas of people with T1D before or around clinical onset of disease, indicating that an association between EV infections and T1D exists. However, definitive evidence for its role as disease triggers is lacking. Recent access to human samples is starting to provide the necessary tools to define their role in disease pathogenesis. Emerging evidence suggests that chronic infections take place in the pancreas of diabetic donors. However, the development of sensitive techniques able to detect low amounts of viral protein and RNA still constitute a major challenge for the field.

Summary

New evidence at the protein, RNA, and host immune response level suggests a role for EV infections in the development of autoimmunity. In the upcoming years, new technologies, collaborative efforts, and therapeutic interventions are likely to find a definitive answer for their role in disease pathogenesis.

(CDC) CDC 23 July 2018. https://www.cdc.gov/non-polio-enterovirus/index.html.

Craig ME, Nair S, Stein H, Rawlinson WD. Viruses and type 1 diabetes: a new look at an old story. Pediatr Diabetes. 2013;14(3):149–58. https://doi.org/10.1111/pedi.12033. CrossRefPubMed

Pons-Salort M, Oberste MS, Pallansch MA, Abedi GR, Takahashi S, Grenfell BT, et al. The seasonality of nonpolio enteroviruses in the United States: patterns and drivers. Proc Natl Acad Sci U S A. 2018;115(12):3078–83. https://doi.org/10.1073/pnas.1721159115.CrossRefPubMedPubMedCentral

Muirhead CR, Cheetham TD, Court S, Begon M, McNally RJ. How do childhood diagnoses of type 1 diabetes cluster in time? PLoS One. 2013;8(4):e60489. https://doi.org/10.1371/journal.pone.0060489.CrossRefPubMedPubMedCentral

Patterson CC, Gyurus E, Rosenbauer J, Cinek O, Neu A, Schober E, et al. Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase. Diabetologia. 2012;55(8):2142–7. https://doi.org/10.1007/s00125-012-2571-8.CrossRefPubMed

Szypowska A, Ramotowska A, Wysocka-Mincewicz M, Mazur A, Lisowicz L, Ben-Skowronek I, et al. Seasonal variation in month of diagnosis of polish children with type 1 diabetes - a multicenter study. Exp Clin Endocrinol Diabetes. 2018; https://doi.org/10.1055/s-0043-125321.

•• Krogvold L, Edwin B, Buanes T, Frisk G, Skog O, Anagandula M, et al. Detection of a low-grade enteroviral infection in the islets of langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes. 2015;64(5):1682–7. https://doi.org/10.2337/db14-1370. This study provides evidence of a low grade enterovirus infection in the pancreas of patients with recent onset T1D. CrossRefPubMed

Baggen J, Thibaut HJ, Strating J, van Kuppeveld FJM. The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol. 2018;16(6):368–81. https://doi.org/10.1038/s41579-018-0005-4.CrossRefPubMed

• Oikarinen M, Tauriainen S, Oikarinen S, Honkanen T, Collin P, Rantala I, et al. Type 1 diabetes is associated with enterovirus infection in gut mucosa. Diabetes. 2012;61(3):687–91. https://doi.org/10.2337/db11-1157. This study detected viral RNA and protein in the gut of patients with T1D. CrossRefPubMedPubMedCentral

10.

Mercalli A, Lampasona V, Klingel K, Albarello L, Lombardoni C, Ekstrom J, et al. No evidence of enteroviruses in the intestine of patients with type 1 diabetes. Diabetologia. 2012;55(9):2479–88. https://doi.org/10.1007/s00125-012-2591-4.CrossRefPubMed

11.

Snell-Bergeon JK, Smith J, Dong F, Baron AE, Barriga K, Norris JM, et al. Early childhood infections and the risk of islet autoimmunity: the diabetes autoimmunity study in the young (DAISY). Diabetes Care. 2012;35(12):2553–8. https://doi.org/10.2337/dc12-0423.CrossRefPubMedPubMedCentral

12.

Rasmussen T, Witso E, Tapia G, Stene LC, Ronningen KS. Self-reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study. Diabetes Metab Res Rev. 2011;27(8):834–7. https://doi.org/10.1002/dmrr.1258.CrossRefPubMed

13.

Beyerlein A, Wehweck F, Ziegler AG, Pflueger M. Respiratory infections in early life and the development of islet autoimmunity in children at increased type 1 diabetes risk: evidence from the BABYDIET study. JAMA Pediatr. 2013;167(9):800–7. https://doi.org/10.1001/jamapediatrics.2013.158.CrossRefPubMed

14.

Beyerlein A, Donnachie E, Jergens S, Ziegler AG. Infections in early life and development of type 1 diabetes. JAMA. 2016;315(17):1899–901. https://doi.org/10.1001/jama.2016.2181.CrossRefPubMed

15.

• Lonnrot M, Lynch KF, Elding Larsson H, Lernmark A, Rewers MJ, Torn C, et al. Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study. Diabetologia. 2017;60(10):1931–40. https://doi.org/10.1007/s00125-017-4365-5. This article shows a positive correlation between recent respiratory infections in young children and an increased risk of islet autoimmunity. CrossRefPubMedPubMedCentral

16.

Stene LC, Oikarinen S, Hyoty H, Barriga KJ, Norris JM, Klingensmith G, et al. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the diabetes and autoimmunity study in the young (DAISY). Diabetes. 2010;59(12):3174–80. https://doi.org/10.2337/db10-0866.CrossRefPubMedPubMedCentral

17.

•• Oikarinen S, Martiskainen M, Tauriainen S, Huhtala H, Ilonen J, Veijola R, et al. Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes. 2011;60(1):276–9. https://doi.org/10.2337/db10-0186. This study reported that EV RNA positive samples are more frequent in case children that progress to type 1 diabetes and that the strongest risk is related to EV positivity 6 months before the appearance of the first autoantibody. CrossRefPubMed

18.

Mustonen N, Siljander H, Peet A, Tillmann V, Harkonen T, Ilonen J, et al. Early childhood infections precede development of beta-cell autoimmunity and type 1 diabetes in children with HLA-conferred disease risk. Pediatr Diabetes. 2018;19(2):293–9. https://doi.org/10.1111/pedi.12547.CrossRefPubMed

19.

•• Ziegler AG, Bonifacio E, Group B-BS. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia. 2012;55(7):1937–43. https://doi.org/10.1007/s00125-012-2472-x. This article reports that the age period 9 months to 2 years is associated with a high incidence of activation of type 1 diabetes associated autoimmunity in genetically at-risk children. CrossRefPubMed

20.

• Krischer JP, Lynch KF, Schatz DA, Ilonen J, Lernmark A, Hagopian WA, et al. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015;58(5):980–7. https://doi.org/10.1007/s00125-015-3514-y. Collaborative study that shows evidence for the appearance of autoantibodies very early in life The incidence of IAA peaks within the first year of life and declines over the following 5 years, but GADA only increases until the second year and remains relatively constant. CrossRefPubMedPubMedCentral

21.

•• Lietzen N, An LTT, Jaakkola MK, Kallionpaa H, Oikarinen S, Mykkanen J, et al. Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes. Diabetologia. 2018;61(2):381–8. https://doi.org/10.1007/s00125-017-4460-7. Innovative study that used genome-wide transcriptomics data to characterise EV-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. CrossRefPubMed

22.

Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, et al. A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes. 2014;63(7):2538–50. https://doi.org/10.2337/db13-1777.CrossRefPubMedPubMedCentral

23.

Kallionpaa H, Elo LL, Laajala E, Mykkanen J, Ricano-Ponce I, Vaarma M, et al. Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes. 2014;63(7):2402–14. https://doi.org/10.2337/db13-1775.CrossRefPubMed

24.

Laiho JE, Oikarinen M, Richardson SJ, Frisk G, Nyalwidhe J, Burch TC, et al. Relative sensitivity of immunohistochemistry, multiple reaction monitoring mass spectrometry, in situ hybridization and PCR to detect Coxsackievirus B1 in A549 cells. J Clin Virol. 2016;77:21–8. https://doi.org/10.1016/j.jcv.2016.01.015.CrossRefPubMedPubMedCentral

25.

•• Genoni A, Canducci F, Rossi A, Broccolo F, Chumakov K, Bono G, et al. Revealing enterovirus infection in chronic human disorders: an integrated diagnostic approach. Sci Rep. 2017;7(1):5013. https://doi.org/10.1038/s41598-017-04993-y. Development of a new RT-PCR and in vitro amplification methods with the aim of increasing the sensitivity for the detection of EVs in clinical samples. CrossRefPubMedPubMedCentral

26.

Philips T, Kusmartseva I, Gerling IC, Campbell-Thompson M, Wasserfall C, Pugliese A, et al. Factors that influence the quality of RNA from the pancreas of organ donors. Pancreas. 2017;46(2):252–9. https://doi.org/10.1097/MPA.0000000000000717. CrossRefPubMedPubMedCentral

27.

Huang X, Yuang J, Goddard A, Foulis A, James RF, Lernmark A, et al. Interferon expression in the pancreases of patients with type I diabetes. Diabetes. 1995;44(6):658–64.CrossRefPubMed

28.

Foulis AK, Farquharson MA, Meager A. Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. Lancet. 1987;2(8573):1423–7.CrossRefPubMed

29.

Newby BN, Mathews CE. Type I interferon is a catastrophic feature of the diabetic islet microenvironment. Front Endocrinol (Lausanne). 2017;8:232. https://doi.org/10.3389/fendo.2017.00232.CrossRef

30.

Newby BN, Brusko TM, Zou B, Atkinson MA, Clare-Salzler M, Mathews CE. Type 1 Interferons potentiate human CD8(+) T-cell cytotoxicity through a STAT4- and Granzyme B-dependent pathway. Diabetes. 2017;66(12):3061–71. https://doi.org/10.2337/db17-0106.CrossRefPubMedPubMedCentral

31.

Morse ZJ, Horwitz MS. Innate viral receptor signaling determines type 1 diabetes onset. Front Endocrinol (Lausanne). 2017;8:249. https://doi.org/10.3389/fendo.2017.00249.CrossRef

32.

Op de Beeck A, Eizirik DL. Viral infections in type 1 diabetes mellitus--why the beta cells? Nat Rev Endocrinol. 2016;12(5):263–73. https://doi.org/10.1038/nrendo.2016.30.CrossRefPubMedCentral

33.

Sarmiento L, Frisk G, Anagandula M, Hodik M, Barchetta I, Netanyah E, et al. Echovirus 6 infects human exocrine and endocrine pancreatic cells and induces pro-inflammatory innate immune response. Viruses. 2017;9(2) https://doi.org/10.3390/v9020025.CrossRefPubMedCentral

34.

Marroqui L, Dos Santos RS, Op de Beeck A, Coomans de Brachene A, Marselli L, Marchetti P, et al. Interferon-alpha mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes. Diabetologia. 2017;60(4):656–67. https://doi.org/10.1007/s00125-016-4201-3.CrossRefPubMed

35.

Freimuth P, Philipson L, Carson SD. The coxsackievirus and adenovirus receptor. Curr Top Microbiol Immunol. 2008;323:67–87.PubMed

36.

Selinka HC, Wolde A, Sauter M, Kandolf R, Klingel K. Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism. Med Microbiol Immunol. 2004;193(2–3):127–31. https://doi.org/10.1007/s00430-003-0193-y.CrossRefPubMed

37.

Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattre P, et al. Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol. 2000;74(21):10153–64.CrossRefPubMedPubMedCentral

38.

• Hodik M, Anagandula M, Fuxe J, Krogvold L, Dahl-Jorgensen K, Hyoty H, et al. Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes. BMJ Open Diabetes Res Care. 2016;4(1):e000219. https://doi.org/10.1136/bmjdrc-2016-000219. This article shows that CAR is expressed in the pancreas and its expression is enhanced in T1D patients, favoring a potential EV infection. CrossRefPubMedPubMedCentral

39.

Ylipaasto P, Klingel K, Lindberg AM, Otonkoski T, Kandolf R, Hovi T, et al. Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia. 2004;47(2):225–39. https://doi.org/10.1007/s00125-003-1297-z.CrossRefPubMed

40.

Petzold A, Solimena M, Knoch KP. Mechanisms of Beta cell dysfunction associated with viral infection. Curr Diab Rep. 2015;15(10):73. https://doi.org/10.1007/s11892-015-0654-x. CrossRefPubMedPubMedCentral

41.

Sarmiento L, Medina A, Aziz K, Anagandula M, Cabrera-Rode E, Fex M, et al. Differential effects of three echovirus strains on cell lysis and insulin secretion in beta cell derived lines. J Med Virol. 2016;88(6):971–8. https://doi.org/10.1002/jmv.24438.CrossRefPubMed

42.

• Ifie E, Russell MA, Dhayal S, Leete P, Sebastiani G, Nigi L, et al. Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells. Diabetologia. 2018; https://doi.org/10.1007/s00125-018-4704-1. This study characterizes the expression of CAR and concludes that CAR-SIV, the predominant isoform of CAR, is expressed in beta cells and is located in the cytoplasm, colocalizing with insulin. CrossRefPubMedPubMedCentral

43.

Marroqui L, Lopes M. dos Santos RS, Grieco FA, Roivainen M, Richardson SJ et al. differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic alpha and beta cells. elife. 2015;4:e06990. https://doi.org/10.7554/eLife.06990. CrossRefPubMedPubMedCentral

44.

• Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia. 2009;52(6):1143–51. https://doi.org/10.1007/s00125-009-1276-0. This study reports that VP1 is commonly found in the islets of recent-onset T1D patients compared to controls. CrossRefPubMed

45.

•• Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, et al. Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes. Diabetologia. 2016;59(11):2448–58. https://doi.org/10.1007/s00125-016-4067-4. This collaborative study analyzed samples from the EADB, nPOD and DiViD cohort. It describes hyperexpression of HLA class I molecules as a defining feature of T1D. CrossRefPubMedPubMedCentral

46.

• Coomans de Brachene A, Dos Santos RS, Marroqui L, Colli ML, Marselli L, Mirmira RG, et al. IFN-alpha induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells. Diabetologia. 2018;61(3):636–40. https://doi.org/10.1007/s00125-017-4536-4. This study shows that HLA-I overexpression can be maintained for long time after the inflammatory stimuli has dissapeared. CrossRefPubMed

47.

Rodriguez-Calvo T, Suwandi JS, Amirian N, Zapardiel-Gonzalo J, Anquetil F, Sabouri S, et al. Heterogeneity and Lobularity of pancreatic pathology in type 1 diabetes during the Prediabetic phase. J Histochem Cytochem. 2015;63(8):626–36. https://doi.org/10.1369/0022155415576543.CrossRefPubMedPubMedCentral

48.

• Honkanen H, Oikarinen S, Nurminen N, Laitinen OH, Huhtala H, Lehtonen J, et al. Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity. Diabetologia. 2017;60(3):424–31. https://doi.org/10.1007/s00125-016-4177-z. This article suggest that EV infections diagnosed by detecting viral RNA in stools are associated with the development of islet autoimmunity with a time lag of several months. CrossRefPubMed

49.

Simonen-Tikka ML, Pflueger M, Klemola P, Savolainen-Kopra C, Smura T, Hummel S, et al. Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study. Diabetologia. 2011;54(12):2995–3002. https://doi.org/10.1007/s00125-011-2305-3.CrossRefPubMed

50.

van der Sanden SM, Koopmans MP, van der Avoort HG. Detection of human enteroviruses and parechoviruses as part of the national enterovirus surveillance in the Netherlands, 1996-2011. Eur J Clin Microbiol Infect Dis. 2013;32(12):1525–31. https://doi.org/10.1007/s10096-013-1906-9.CrossRefPubMed

51.

Tan CY, Ninove L, Gaudart J, Nougairede A, Zandotti C, Thirion-Perrier L, et al. A retrospective overview of enterovirus infection diagnosis and molecular epidemiology in the public hospitals of Marseille, France (1985-2005). PLoS One. 2011;6(3):e18022. https://doi.org/10.1371/journal.pone.0018022.CrossRefPubMedPubMedCentral

52.

Laitinen OH, Honkanen H, Pakkanen O, Oikarinen S, Hankaniemi MM, Huhtala H, et al. Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that portends type 1 diabetes. Diabetes. 2014;63(2):446–55. https://doi.org/10.2337/db13-0619.CrossRefPubMed

53.

Gamble DR, Kinsley ML, FitzGerald MG, Bolton R, Taylor KW. Viral antibodies in diabetes mellitus. Br Med J. 1969;3(5671):627–30.CrossRefPubMedPubMedCentral

54.

Pugliese A, Yang M, Kusmarteva I, Heiple T, Vendrame F, Wasserfall C, et al. The Juvenile Diabetes Research Foundation network for pancreatic organ donors with diabetes (nPOD) program: goals, operational model and emerging findings. Pediatr Diabetes. 2014;15(1):1–9. https://doi.org/10.1111/pedi.12097.CrossRefPubMed

55.

Pugliese A, Vendrame F, Reijonen H, Atkinson MA, Campbell-Thompson M, Burke GW. New insight on human type 1 diabetes biology: nPOD and nPOD-transplantation. Curr Diab Rep. 2014;14(10):530. https://doi.org/10.1007/s11892-014-0530-0. CrossRefPubMedPubMedCentral

Titel: Enteroviral Infections as a Trigger for Type 1 Diabetes
verfasst von: Teresa Rodriguez-Calvo
Publikationsdatum: 01.11.2018
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 11/2018
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-018-1077-2

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Enteroviral Infections as a Trigger for Type 1 Diabetes

Abstract

Purpose of Review

Recent Findings

Summary

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Hinter dieser Appendizitis steckte ein Erreger

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2018

Diabetes and HIV

Ketosis-Prone Diabetes (Flatbush Diabetes): an Emerging Worldwide Clinically Important Entity

The Role of Accessory Cells in Islet Homeostasis

The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms

Vegetarian Diets and the Risk of Diabetes

Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Hinter dieser Appendizitis steckte ein Erreger

Update Innere Medizin