Detection of Coxsackie B Virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus

Andréoletti, Laurent; Hober, Didier; Hober-Vandenberghe, Christine; Belaïch, S; Vantyghem, Marie-Christine; Lefèbvre, J; Wattré, P

doi:10.1002/(sici)1096-9071(199706)52:2<121::aid-jmv1>3.0.co;2-5

Cited by 145 publications

(92 citation statements)

References 25 publications

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“…The figure for positivity rose to 37% in children of 3 years of age or younger. These results have been confirmed in a number of other studies in France [30], Sweden [31,32] and in Australia [33]. In the results from Sweden and France, whole blood was the starting point for the work and the percentage positivity rose considerably (Table 2).…”

Section: Coxsackie B Virusessupporting

confidence: 63%

“…In one set of results using PCR methodology, it has been shown that positivity for enteroviruses was quite commonly present in adult insulin-dependent diabetic patients at onset [30]. In a small number of patients, previously diagnosed with insulin dependent diabetes, enterovirus sequences could also be detected, raising the possibility of a continuing infection.…”

Section: Significance Of Tests To Detect Virusessupporting

confidence: 55%

“…Non-insulin dependent diabetic patients were negative for enteroviruses when tested in this system. [30] 1997 whole blood adults coxsackie B3B4 [29] 1999 serum children younger than 15 years of age coxsackie B viruses and echoviruses [23] 2000 whole blood children and adults coxsackie B2B3B4 [34] 2000 serum prediabetic children not determined [35] 2000 serum prediabetic children not determined [33] 2000 serum diabetic children - [31] 2001 mononuclear cells diabetic children coxsackie B4B5 cells enterovirus infection has been associated with the onset of insulin requiring diabetes. In an earlier review of 11 such cases who were mainly children, all six coxsackie viruses were implicated.…”

Section: Significance Of Tests To Detect Virusesmentioning

confidence: 99%

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The role of viruses in human diabetes

Hyöty

2002

Diabetologia

221

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Abstract. Viruses have long been considered a major environmental factor in the aetiology of Type I (insulin-dependent) diabetes mellitus and recent work has greatly confirmed and extended this role. In addition to the enteroviruses, there are several other viruses which, from time to time, have been considered potential causal agents for human diabetes. With the exception of rubella, their role is not clear.

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Section: Coxsackie B Virusessupporting

confidence: 63%

Section: Significance Of Tests To Detect Virusessupporting

confidence: 55%

Section: Significance Of Tests To Detect Virusesmentioning

confidence: 99%

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The role of viruses in human diabetes

Hyöty

2002

Diabetologia

221

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“…Much of the evidence is circumstantial [1] but includes observations that antibodies against common Coxsackie B enteroviruses (CVB) and enteroviral RNA occur more frequently in the circulation of recent-onset type 1 diabetes patients than in controls [2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

et al. 2009

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Aims/hypothesis Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls. Methods Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I. Results vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets. Conclusions/interpretation Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.

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“…In another study, CVB genome was detected in five out of 12 (42%) newly diagnosed T1D patients and in one of 12 (8%) patients during the course of the disease. By contrast, none of 12 T2D patients and none of 15 healthy adults had enterovirus sequences in their blood [43]. The CVB4 strain E2 is able to induce a persistent infection of human islet b cells [44], whereas a new isolated CVB4 variant, VD2921, causes a persistent infection of islet b cells with a consequent disturbance of proinsulin synthesis and insulin secretion [45].…”

Section: Environmental Factorsmentioning

confidence: 97%

Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes

Geenen

Mottet

Dardenne

et al. 2010

Current Opinion in Pharmacology

Self Cite

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Before being able to react against infectious nonself-antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programing central self-tolerance to pancreatic insulin-secreting islet b cells, leading to the breakdown of immune homeostasis with an enrichment of islet b-cell reactive effector T cells and a deficiency of b-cell specific natural regulatory T cells (nTregs) in the peripheral Tlymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. The very low degree of insulin gene transcription in normal murine and human thymus explains why the insulin protein is poorly tolerogenic as demonstrated in many studies, including the failure of all clinical trials that have attempted immune tolerance to islet b cells via various methods of insulin administration. On the basis of the close homology and crosstolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called 'negative/tolerogenic selfvaccination', is currently being developed for the prevention and cure of T1D. If this approach were found to be effective for reprograming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organspecific autoimmune diseases. ''Autoimmune disease can be a depressing subject. In Shakespearian terms, 'it is a tale told by an idiot. . .signifying nothing'. In more modern metaphor, it is an error made at random in an enormous, delicately programmed computer. Nature has no other way of handling genetic error than by eliminating the faulty, and the physician handling autoimmune diseases can expect no help from her.'' Sir F. MacFarlane Burnet, 1972 IntroductionIn 1965, our late Belgian colleague Willy Gepts observed inflammatory infiltrates of mononuclear cells invading Langerhans' islets in the pancreas of deceased young diabetic patients [1]. In a prophetical analysis, he discussed his innovative results with the following words: 'It seems probable that, in the pancreas of acute diabetics, we had the opportunity to catch the final stages of a process which has been going on for an indefinite time, perhaps from birth on'. Since this pioneering work, research conducted worldwide has firmly established that type 1 diabetes (T1D) -previously called juvenile diabetes, and insulin-dependent diabetes -is the final result of a highly selective autoimmune response that generates an inflammation (insulitis), followed by the death of insulin-secreting islet b cells in the pancreas. Incidence of T1D peaks around 10-14 years and this disease affects AE20 million people worldwide (approximately 10%...

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Detection of Coxsackie B Virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus

Cited by 145 publications

References 25 publications

The role of viruses in human diabetes

The role of viruses in human diabetes

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes

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