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  • 1
    Electronic Resource
    Electronic Resource
    Cell-Mediated autoimmunity at the onset of insulin-dependent diabetes mellitus (IDDM) (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 546-550 
    Details
    ISSN: 1432-1440
    Keywords: Type I diabetes ; Autoimmunity ; Ia-antigen bearing cells ; ICA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral blood lymphocytes have been investigated in 20 newly diagnosed type-I diabetics and 10 healthy subjects using monoclonal antibodies. Mononuclear cells were marked with anti-T-lymphocytes (Leu2, 3, 4, 12) and anti-Ia-antibodies (K14, L243) using indirect immunofluorescence. The percentage of circulating K14- and L243-positive cells was significantly higher in all diabetics than in normal controls. An increase in the number of K14-bearing cells was found in newly diagnosed patients with duration of less than 7 days (n=10) compared with diabetics of longer duration (1 to 8 months;n=10). Using dual-color immunofluorescence with fluorescein-conjugated anti-T-lymphocytes and rhodamin-conjugated anti-Ia-antibodies it was not possible to identify Ia-antigen bearing cells (Ia cells) as helper or suppressor lymphocytes. In addition, there was no significant difference in the number of Ia cells in diabetics with and without islet cell antibodies. It is concluded that there is evidence of activation of cellular immune response in type I diabetes, particularly in the early days of manifestation. However, previous assumptions that Ia cells represent T-cell activation have to be questioned.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01727620
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Development of celiac disease-associated antibodies in offspring of parents with Type I diabetes (2000)
    Springer
    Diabetologia 43 (2000), S. 1005-1011 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Celiac disease ; Type I diabetes ; transglutaminase ; antibody screening ; islet antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The aim of this study was to determine the frequency and temporal development of antibodies related to celiac disease in offspring of parents with Type I (insulin-dependent) diabetes mellitus. Methods. Sera from 913 offspring of parents with Type I diabetes prospectively followed from birth to the age of 8 years were tested for IgG-transglutaminase antibodies (IgG-tTGCAs), endomysial IgA antibodies (EMA) and gliadin antibodies. Results. We found tTGCAs in 32 (3.5 %) of the 913 relatives. Prevalence was related to age and reached 6.5 % at age 8 years. Endomysial IgA antibodies were detected in 44 % of the relatives with tTGCAs and 0.6 % of tTGCA negative relatives and were also most prevalent (5 %) in those aged 8 years. Both tTGCAs and EMAs were more frequent in relatives with the HLA DRB1*03 DQA1*0501 DQB1*02 haplotype (7.1 % and 7.2 %, respectively; p 〈 0.005). Anti-gliadin antibodies were common in both tTGCA positive (42 %) and negative (23 %) relatives, did not show a relation with age and were less prevalent in relatives with HLA DR3 (p 〈 0.05). There was no association between the presence of antibodies associated with celiac disease and islet autoantibodies in these relatives. Of the relatives 15 (1.6 %) had tTGCAs plus EMAs. In two of these, anti-gliadin antibodies were detected before the detection of tTGCAs and EMAs at the age of 9 months whereas none of the remainder had any antibodies associated with celiac disease before age 2 years. In three there were no detectable anti-gliadin antibodies in any of the samples tested. Celiac disease without clinical symptoms was diagnosed in 9 of 12 by intestinal biopsy. Conclusion/interpretation. A statistically significant proportion of relatives of patients with Type I diabetes have celiac disease-associated autoimmunity and the silent form of celiac disease early in life. These relatives should, therefore, be considered for celiac antibody screening. [Diabetologia (2000) 43: 1005–1011]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051483
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  • 3
    Electronic Resource
    Electronic Resource
    Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study (1999)
    Springer
    Diabetologia 42 (1999), S. 671-677 
    Details
    ISSN: 1432-0428
    Keywords: Keywords HLA genotype ; Type I diabetes ; islet autoimmunity ; autoantibody appearance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus. The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity. Methods. HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up: 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age. Results. The HLA genotypes DRB1 * 03/04(DQB1 *57non-Asp) and DRB1 * 04/04(DQB1*57non-Asp) were present in 7.1 % and 5.0 % of offspring of parents with Type I diabetes. The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3 % vs 5.5 %, odds ratio 6.3 [p = 0.002] and 22.7 % vs 4.2 %, odds ratio 6.6 [p = 0.003]) and half of all offspring who developed antibodies had these genotypes. Other genotypes were not associated with an increase in risk. By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20 % (95 % CI 9.4,30.6) for offspring carrying either the DRB1 * 03/04(DQB1 *57non-Asp) or the DRB1 * 04/04(DQB1*57non-Asp) genotype compared with 2.7 % (95 % CI 1.2,4.2) for offspring without these genotypes (p 〈 0.0001). Conclusion/interpretation. These data show that early appearance of islet autoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homozygous offspring and indicate that primary prevention could be considered once available in an offspring cohort selected for these genotypes. [Diabetologia (1999) 42: 671–677]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051214
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 970-975 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; nervous tissue autoantibodies ; islet cell antibodies.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26 ± 6 years) and 48 long-term IDDM patients (age 40 ± 13 years, duration of diabetes 22 ± 12 years) without myocardial perfusion abnormalities (normal 99 mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40 %) and 12 long-term (25 %) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5 %; p 〈 0.01, p 〈 0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r = 0.34, p = 0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy ( ≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41 %) and 3 (12 %), respectively were positive for CF-SG autoantibodies (p = 0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM. [Diabetologia (1996) 39: 970–975]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403917
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 970-975 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; metaiodobenzylguanidine ; autonomic neuropathy ; nervous tissue autoantibodies ; islet cell antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26±6 years) and 48 long-term IDDM patients (age 40±13 years, duration of diabetes 22±12 years) without myocardial perfusion abnormalities (normal 99mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40%) and 12 long-term (25%) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5%; p〈0.01, p〈0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r=0.34, p=0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy (≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41%) and 3 (12%), respectively were positive for CF-SG autoantibodies (p=0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403917
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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