No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7?19 years

Scherbaum, Werner A.; Hampl, Walter; Muir, Peter; Glück, Michael; Seißler, Jochen; Egle, H.; Hauner, Hans; Boehm, B. O.; Heinze, E.; Banatvala, J. E.; Pfeiffer, E. F.

doi:10.1007/bf00408360

Cited by 14 publications

(3 citation statements)

References 19 publications

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“…One report suggested that ICA occur with a higher frequency in those diabetic patients with moderate to high CB4 antibody titres [88]. With mumps infection the ICA induced are not always associated with diabetes [89].…”

Section: Autoimmunity and Virusesmentioning

confidence: 99%

Diabetes mellitus due to viruses ? some recent developments

et al. 1993

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Many different viruses belonging to several genera have the potential to damage beta cells. The mechanisms they employ are varied, and infection may result in either a direct destruction of islets and rapid insulin deficiency, or in a more gradual loss of functioning islets with the onset of diabetes many years later. Several case histories involving extensive cytolysis of beta cells can be directly linked to viral infection, whilst an example of diabetes occurring many years after viral infection is found in individuals who had a congenital infection with rubella virus. Here, the virus induces an autoimmune reaction against beta cells. Autoimmune phenomena have also been observed in islets following infections with viruses other than rubella, and thus activation of autoimmune mechanisms leading to beta-cell destruction may be a relatively frequent occurrence. Recent evidence shows that picornaviruses are not exclusively lytic, and can induce more subtle, long-term changes in beta cells, which may be important in the aetiology of diabetes. The exact mechanisms involved are not known, but it is clear that several viruses can directly inhibit insulin synthesis and induce the expression of other proteins such as interferons, and the HLA antigens. Strain differences in viruses are important since not all variants are tropic for the beta cells. Several laboratories are in the process of identifying the genetic determinants of tropism and diabetogenicity, especially amongst the Coxsackie B (CB) virus group. The sequence of one such diabetogenic CB4 strain virus has been determined.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Autoimmunity and Virusesmentioning

confidence: 99%

Diabetes mellitus due to viruses ? some recent developments

et al. 1993

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“…Separate aspects of this study have been published recently [12,13]. Here we addressed the question of whether the detection of antibodies to the 64K protein or other Type 1 diabetes specific autoantibodies can be correlated with genetic high risk markers and impaired Beta-cell function.…”

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confidence: 99%

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

et al. 1992

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Summary.A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6 %). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50 % of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ 13 chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type i (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals.

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“…The enzyme glutamic acid decarboxylase (GAD65) has recently been recognized as a major autoantigen in insulindependent diabetes mellitus [1][2][3]. A T-cell response corresponding to carboxyterminal epitopes of the GAD-molecule was found to characterize the pre-diabetic phase in the NOD mouse model [4,5].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Stimulation with Glutamic Acid Decarboxylase (GAD65) Leads to an Oligoclonal Response of Peripheral T‐Cells in an IDDM Patient

et al. 1995

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The enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). To study T-cell reactivity towards GAD, peripheral blood leucocytes from seven patients with IDDM and five control subjects were stimulated in vitro with recombinant GAD. All diabetics studied were heterozygous for diabetes-associated HLA alleles, i.e. HLA-DRB1*03,*04-DQB1 *0302,*0201. A single IDDM subject (no. GAD65.05) revealed a strong response against GAD65. After stimulation, his T-cell receptor beta (TCRBV) usage was found to be oligoclonal. The sequence analysis of the putative peptide binding region of the T-cell receptor (CDR3 region) of 37 GAD-reactive T-cell clones revealed no common CDR3 motif. The stimulation of GAD-reactive T-cells could be inhibited with anti-class II monoclonal antibodies, indicating a class II restricted T-cell response. In addition, GAD65-responsive T-cells revealed a Th1 cytokine response pattern. The author's data suggest that GAD-reactive T-cells of Th1 phenotype can be obtained after in vitro stimulation of peripheral blood leucocytes from an HLA-DRB1*03/*04 heterozygous IDDM patient. The lack of a common CDR3 motif suggests the absence of an immunodominant T-cell epitope in that patient, or may indicate receptor repertoire spreading of peripheral T-lymphocytes.

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No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7?19 years

Cited by 14 publications

References 19 publications

Diabetes mellitus due to viruses ? some recent developments

Diabetes mellitus due to viruses ? some recent developments

Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

In Vitro Stimulation with Glutamic Acid Decarboxylase (GAD65) Leads to an Oligoclonal Response of Peripheral T‐Cells in an IDDM Patient

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