Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes

Hober, Didier; Sané, Famara; Jaïdane, Hela; Riedweg, Karena; Goffard, Anne; Desailloud, Rachel

doi:10.1111/j.1365-2249.2011.04559.x

Cited by 50 publications

(40 citation statements)

References 38 publications

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“…If the regulatory response is insufficient, the recurring immune events could eventually lead to the destruction of the majority of the islet β-cell mass and thereby reduce the body's capacity to produce insulin [30][31][32]. Understanding and mapping the precise kinetics of the immune response to the disease has implications for the design of immunomodulatory therapeutics, and the regulatory immune components of T1D could be therapeutically exploited to ultimately suppress the progression of T1D [33][34][35]. However, the temporal and compositional details of the immune regulation that are associated with the onset and progress of T1D remain controversial [2,36].…”

Section: Discussionmentioning

confidence: 99%

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Farhan¹,

Alghasham²,

Zafar³

et al. 2013

J Diab Res Clin Met

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Background: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease with autoantibodies against glutamic-aciddecarboxylase (GAD)65, insulin and tyrosine phosphatase (TP) as a feature of disease. The correlations of these autoantibodies with disease severity remain to be explored. Here we investigate the status and contribution of autoantibodies against GAD65, insulin and TP in T1D patients and to explore whether these antibodies have a role in T1D progression and in T1D associated neuropathy. Methods: Sera from 57 T1D patients with varying levels of disease activities and 42 age-and sex-matched healthy controls were evaluated for anti-GAD65-antibodies, anti-insulin-antibodies and anti-TP-antibodies. Results: Serum analysis showed T1D patients contain 42% of anti-GAD65-antibodies, 76% of anti-insulin-antibodies and 34% of anti-TP-antibodies. Interestingly, not only was there an increased number of subjects positive for these antibodies, but also levels of these antibodies were significantly higher among T1D patients whose ages were >35 years as compared with younger T1D patients (age ≤35 years). In addition, significant correlation was observed between the levels of these antibodies and glycosylated haemoglobin (HbA 1c ). Furthermore, T1D neuropathic patients had higher levels of these antibodies compared with T1D patients without neuropathy. Conclusions: Our data support an association between these markers autoantibodies and severity of T1D. The stronger response observed in patients with uncontrolled T1D suggests that these antibodies may be useful biomarkers in evaluating the progress of T1D and in elucidating the mechanisms of disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Farhan¹,

Alghasham²,

Zafar³

et al. 2013

J Diab Res Clin Met

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“…Other potential pathogenic mechanisms are the impairment of central self-tolerance due to viral infections [16] and the induction of a subset of antibodies able to favour a viral escape from the immune response, thus participating to the spreading of viruses to beta cells [17].…”

Section: Introductionmentioning

confidence: 99%

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

et al. 2013

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Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients’sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients’ sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

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“…The majority of individuals with these genetic risk factors do not develop T1D and several environmental factors have been considered including infections (6,13,34,40), climate (35), diet (3,21), and stress (16). The possible influence of viral infections as a trigger of islet autoimmunity or clinical onset of T1D has been reported in numerous studies (5,19). …”

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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Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes

Cited by 50 publications

References 38 publications

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

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

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