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  • 1
    Electronic Resource
    Electronic Resource
    Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate (2003)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 17 (2003), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Osteoporosis is a frequent complication in Crohn's disease. Although the efficacy of both sodium fluoride and aminobisphosphonates in postmenopausal osteoporosis has been investigated in long-term therapy studies, no long-term results are available regarding the effect of these agents in the management of osteoporosis in patients with Crohn's disease.Methods : Eighty-four patients with Crohn's disease and pathological bone mineral density findings were randomized to receive either vitamin D3 (1000 IU) and calcium citrate (800 mg) daily (group A) or sodium fluoride (25 mg b.d., group B) or intravenous ibandronate (1 mg every 3 months, group C) in addition to daily calcium/vitamin D substitution. On admission to the study and after 12 and 27 months, patients underwent dual-energy X-ray absorptiometry and radiological examination of the spine.Results : Sixty-eight patients completed the 1-year observation period and were available for the intention-to-treat analysis. No new vertebral fractures were diagnosed. In group A, lumbar bone density increased by 2.6% (P = 0.066, N.S.), in group B by 5.7% (P = 0.003) and in group C by 5.4% (P = 0.003). Therapy with sodium fluoride was associated with an increase in osteocalcin (N.S.), whereas administration of ibandronate was associated with a decrease in the resorption parameter, carboxy-terminal cross-linked type-I collagen telopeptide (P 〈 0.05). Both sodium fluoride and ibandronate resulted in significant decreases in the serum concentration of osteoprotegerin after 9 months (P 〈 0.001).Conclusions : The findings of the present study show that both sodium fluoride and ibandronate are effective in combination with calcium and vitamin D substitution in the management of osteopenia and osteoporosis in patients with Crohn's disease. Both agents are safe and well tolerated, and induce continuous increases in lumbar bone density.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2003.01448.x
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  • 2
    Electronic Resource
    Electronic Resource
    In Vitro Stimulation with Glutamic Acid Decarboxylase (GAD65) Leads to an Oligoclonal Response of Peripheral T-Cells in an IDDM Patient (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 42 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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-DQBl*0302, *0201. A single IDDM subject (no. GAD65.05) revealed a strong response against GAD65. After stimulation, his T-cell receptor β (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 Thl cytokine response pattern. The author's data suggest that GAD-reactive T-cells of Thl phenotype can be obtained after in vitro stimulation of peripheral blood leucocytes from an HLA-DRBl*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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03710.x
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  • 3
    Electronic Resource
    Electronic Resource
    Prevalence of HLA-DQ beta chain non-asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset (1991)
    Springer
    Journal of molecular medicine 69 (1991), S. 687-689 
    Details
    ISSN: 1432-1440
    Keywords: Adult-onset diabetes ; HLA-DQβ ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Particular HLA-DQβ chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogenous German population, we studied HLA-DR specificities and HLA-DQβ chain alleles in young-onset (〈21 years of age;n=185) and adult-onset (〉40 years of age;n=48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQβ chain was significantly associated with type I diabetes in both cohorts (etiologic fraction:93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQβ chain provides a molecular risk marker for type I diabetes of both and adult onset.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01649437
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  • 4
    Electronic Resource
    Electronic Resource
    Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function (1992)
    Springer
    Diabetologia 35 (1992), S. 550-554 
    Details
    ISSN: 1432-0428
    Keywords: Population study ; 64K antibodies ; islet cell antibodies ; complement-fixing islet cell antibodies ; insulin autoantibodies ; HLA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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 β 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 1 (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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400483
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  • 5
    Electronic Resource
    Electronic Resource
    Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes (2000)
    Springer
    Diabetologia 43 (2000), S. 210-217 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Glutamate decarboxylase, autoantibodies, epitope-specificity, Type I diabetes, polyendocrine autoimmune syndrome, stiff-man syndrome, prediabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The aim of this study was to analyse the conformational and linear epitope profiles of glutamic acid decarboxylase antibody (GAD65-ab)-positive sera to find disease-specific epitope profiles and to study, whether GAD65-ab epitope recognition changes or spreads during the prediabetic period and, thus, can provide markers to differentiate early from later stages of progression to diabetes.¶Methods. Sera from subjects before (n = 21), at onset (n = 44), or at increased risk of Type I (insulin-dependent) diabetes mellitus (n = 20) and from patients with stiff-man syndrome (SMS, n = 18) or polyendocrine autoimmune syndrome (PAS, n = 21) were analysed for conformational and linear GAD65 epitope recognition by an immunohistochemical blocking test based on human monoclonal GAD65-ab (MICA 1–10) and western blotting of a GAD65 epitope-cDNA-library.¶Results. A redundant reactivity of many GAD65-ab positive sera to three major conformational (EP-1, EP-2, EP-3) and two dominant linear epitope clusters (amino acid 1–124 and 535–585) was observed in diabetes, polyendocrine autoimmune syndrome and stiff-man syndrome and no disease-specific epitopes or epitope-profiles were detected. Epitope recognition broadened with higher titres and with the vulnerability of patients to acquire additional autoimmune diseases apart from diabetes. Low GAD65-ab serum titres ( 〈 1200 arbitrary units) and EP-1 recognition in the absence of EP-2 binding characterised the early immune response. Changing epitope profiles combined stable recognition of EP-1 with gain or loss of reactivity to C-terminal epitopes during follow-up.¶Conclusion/interpretation. A maturing autoantibody response, which could spread from EP-1-recognition to other regions of GAD65, resulted in titre-related rather than disease-specific epitope profiles which were not sufficient to predict whether GAD65-ab positive subjects will progress to Type I diabetes, autoimmune polyendocrine syndrome or stiff-man syndrome. [Diabetologia (2000) 43: 210–217]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050031
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  • 6
    Electronic Resource
    Electronic Resource
    No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7–19 years (1991)
    Springer
    Diabetologia 34 (1991), S. 835-838 
    Details
    ISSN: 1432-0428
    Keywords: Viral antibodies ; Beta-cell function ; population study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408360
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  • 7
    Electronic Resource
    Electronic Resource
    Molecular aspects of endocrine autoimmunity (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 79-81 
    Details
    ISSN: 1432-1440
    Keywords: Autoimmunity ; Autoantibodies ; Molecular biology ; Insulin-dependent diabetes mellitus ; Thyroid autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00210975
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  • 8
    Electronic Resource
    Electronic Resource
    HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 221-225 
    Details
    ISSN: 1432-1440
    Keywords: Autoantibodies ; Autoimmune thyroid diseases ; Human leukocyte antigen ; Microsomal thyroid antigen ; Thyroid autoimmunity ; Thyroid peroxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area. Of the blood donors, 153 (5.1 %) were found to have high titer of mic-TPO (〉 350 IU/ml). Only two auto-antibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively. Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n=1,863). Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives. Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype. We conclude that a high prevalence of hightiter mic-TPO can be found in healthy blood donors. Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180105
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  • 9
    Electronic Resource
    Electronic Resource
    HLA-DRB3 gene alleles in Caucasian patients with Graves' disease (1992)
    Springer
    Journal of molecular medicine 70 (1992), S. 956-960 
    Details
    ISSN: 1432-1440
    Keywords: Graves' disease ; HLA-DRB3 alleles ; Endocrine ophthalmopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P〈0.001). HLA-DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P〈 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P〈0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P〈0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180447
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  • 10
    Electronic Resource
    Electronic Resource
    Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study (1991)
    Springer
    Journal of molecular medicine 69 (1991), S. 736-741 
    Details
    ISSN: 1432-1440
    Keywords: CIAA ; CF-ICA ; Beta-cell function ; IVGTT ; HLA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01797611
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