Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16

Cabrera-Rode, Eduardo; Sarmiento, Luis; Tiberti, Claudio; Molina, Gisela; Barrios, Julio César Quiroz; Hernández, D.; Diaz-Horta, Oscar; Mario, U. Di

doi:10.1007/s00125-003-1179-4

Cited by 61 publications

(47 citation statements)

References 37 publications

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“…A fluctuating pattern of infectious diseases, including zoonoses (29), has been suggested to contribute to the appearance of either islet autoimmunity, T1D, or both (4,34). The Ljungan virus (LV), a parechovirus, possibly pathogenic to humans (8,23,28) has been proposed to contribute to T1D.…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

et al. 2013

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Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA).LVAb at 75 th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4 th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4 th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X ( p < 0.0001). Furthermore, in the group with 4 th quartile LVAb, 55% were IAA positive ( p = 0.01) and correlation was found between 4 th quartile LVAb and IAA in children < 10 years of age ( p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4 th quartile LVAb correlated with IAA; and 3) there was a correlation between 4 th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.

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Section: Introductionmentioning

confidence: 99%

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

et al. 2013

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“…Coxsackieviruses are capable of infecting human pancreas [2,9], and recent in situ hybridisation studies on post mortem pancreatic specimens of type 1 diabetes patients revealed enterovirus-positive cells exclusively in islet cells [9]. In prospective seroepidemiological studies, several enteroviruses have been associated with type 1 diabetes [4,5,[10][11][12]. Likewise, cultured primary human beta cells are highly susceptible to infections caused by several enterovirus serotypes, representing different genetic subgroups and known to act through a number of different receptor families [9].…”

Section: Introductionmentioning

confidence: 99%

“…IFIT1: 2 and 4 interferon-induced protein with tetratricopeptide repeats 1, 2 and 4 . IFITM1: interferon-induced transmembrane protein 1 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) . IFNB1: interferon β1, fibroblast .…”

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confidence: 99%

Global profiling of coxsackievirus- and cytokine-induced gene expression in human pancreatic islets

et al. 2005

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Aims/hypothesis: It is thought that enterovirus infections initiate or facilitate the pathogenetic processes leading to type 1 diabetes. Exposure of cultured human islets to cytolytic enterovirus strains kills beta cells after a protracted period, suggesting a role for secondary virusinduced factors such as cytokines. Methods: To clarify the molecular mechanisms involved in virus-induced beta cell destruction, we analysed the global pattern of gene expression in human islets. After 48 h, RNA was extracted from three independent human islet preparations infected with coxsackievirus B5 or exposed to interleukin 1β (50 U/ml) plus interferon γ (1,000 U/ml), and gene expression profiles were analysed using Affymetrix HG-U133A gene chips, which enable simultaneous analysis of 22,000 probe sets. Results: As many as 13,077 genes were detected in control human islets, and 945 and 1293 single genes were found to be modified by exposure to viral infection and the indicated cytokines, respectively. Four hundred and eighty-four genes were similarly modified by the cytokines and viral infection. Conclusions/ interpretation: The large number of modified genes observed emphasises the complex responses of human islet cells to agents potentially involved in insulitis. Notably, both cytokines and viral infection significantly (p<0.02) increased the expression of several chemokines, the cytokine IL-15 and the intercellular adhesion molecule ICAM-1, which might contribute to the homing and activation of mononuclear cells in the islets during infection and/or an early autoimmune response. The present results provide novel insights into the molecular mechanisms involved in viral-and cytokine-induced human beta cell dysfunction and death.

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“…In another recent study, performed in different European populations, CBV1 was again associated with increased risk of T1D [54]. In addition, some EVs other than CBVs (mainly certain echoviruses) have been linked to T1D in some studies [55]. Altogether, one can conclude that CBVs are currently the chief candidates for diabetogenic EV types in man.…”

Section: Type Of Diabetogenic Evsmentioning

confidence: 92%

Virus Infections as Potential Targets of Preventive Treatments for Type 1 Diabetes

Nurminen

Oikarinen²,

Hyöty

2012

Rev Diabet Stud

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Environmental factors play an important role in the pathogenesis of type 1 diabetes, and are attractive targets for preventive interventions. Several studies have shown that viruses can cause diabetes in animals, indicating their potential as candidates for environmental triggering agents. However, human studies have been hampered by the complex nature of the disease pathogenesis, leaving the question of viral etiology unanswered. Significant progress has recently been made in this field by searching for viruses within pancreatic tissue samples, and by carrying out prospective studies. Consequently, there is increasing evidence for a group of enteroviruses acting as possible environmental key triggers. In past studies, these viruses have been linked to type 1 diabetes. Recent studies have shown that they exert tropism to pancreatic islets, and that they are associated with the start of the beta-cell damaging process. Also, polymorphisms of the gene coding for the innate immune system sensor for enteroviruses (IFIH1) were found to modulate the risk of diabetes. Based on these findings, interest in the possible development of vaccines against these viruses has increased. However, even if enterovirus vaccines (polio vaccines) are effective and safe, we currently lack necessary information for the development of a vaccine against diabetogenic enteroviruses, e.g. regarding the identification of their specific serotypes and the causal relationship between these viruses and diabetes initiation. Ongoing research projects are currently addressing these questions, and will hopefully increase the consensus in this field. Also, new sequencing technologies will provide additional information about the whole virome, which could enable the discovery of new candidate viruses.

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Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16

Cited by 61 publications

References 37 publications

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

Relationship Between Ljungan Virus Antibodies, HLA-DQ8, and Insulin Autoantibodies in Newly Diagnosed Type 1 Diabetes Children

Global profiling of coxsackievirus- and cytokine-induced gene expression in human pancreatic islets

Virus Infections as Potential Targets of Preventive Treatments for Type 1 Diabetes

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