1,721,045 research outputs found

    Tissue transglutaminase autoantibody detection in human saliva: a powerful method for celiac disease screening

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    Objective To test the possibility of detecting tissue transglutaminase autoantibodies (tTG-Abs) in saliva with a novel sensitive fluid-phase radioimmunoassay (RIA). Study design Paired saliva and serum samples from 39 patients with celiac disease (CD), at the first biopsy (Group 1: 28 females, mean age 11.5 ± 11.1 years); 32 controls with a normal duodenal mucosa (Group 2: 18 females, mean age 8.1 ± 3.6 years); and 32 healthy volunteers (Group 3: 21 females, mean age 31.7 ± 9.8 years) were studied for tTG-Ab presence. Limit of positivity for salivary assay was calculated according to the 99th percentiles of Group 2 control children and was expressed as an autoantibody (Ab) index. Results Salivary tTG-Abs were found in 97.4% of the patients with CD and in 100% of the corresponding serum samples. All Group 3 subjects were negative with both saliva and serum assays. A correlation between saliva and serum tTG-Ab titers was found (r = 0.826, P = .0014). Conclusions This study demonstrates that it is possible to detect salivary tTG-Abs in CD with a non-invasive, simple to perform, reproducible and sensitive method

    Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.

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    The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1D

    Humoral and cellular immune abnormalities in neonates of diabetic mothers: any pathological role?

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    Insulin antibodies, insulin complexes, T-cell subsets and T-cells bearing surface antigens indicating early activation were studied in 35 and 24 infants of diabetic and of normal mothers respectively, which were compared with normal adult control subjects. Anti-insulin antibodies were evaluated using a modified version of Andersen's method, insulin complexes were assessed by a method developed by us; total T cells, helper/inducer and cytotoxic/suppressor T lymphocytes, and early activated T lymphocytes were determined using the monoclonal antibodies OKT3, OKT4, OKT8 and 4F2 respectively. The presence of insulin antibodies was correlated to macrosomia, hypoglycaemia and respiratory distress syndrome. Insulin-anti-insulin complexes were found in some of the neonates and were likely to have been formed by maternal antibodies and insulin from the neonate. Modifications of T-cell subsets were found in the neonates both of diabetic and of normal mothers. --Despite the presence of these immune abnormalities in some infants of diabetic mothers, the clinical onset of diabetes was not diagnosed in any of the cases studied. Nevertheless, the immunological abnormalities in neonates of diabetic mothers have short-term pathogenetic effects which raises the question of their possible long-term effect

    Insulin prophylaxis down-regulates islet antigen expression and islet autoimmunity in the low-dose STZ mouse model of diabetes

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    The aims of this study were to evaluate in an autoimmune diabetes animal model [low-dose streptozotocin (LD-STZ) mouse] (a) the efficacy of a prophylactic insulin treatment as a diabetes prevention tool, and (b) its possible mechanisms through both the insulitis evaluation and islets antigen expression, Diabetes was induced in male C57B16/J mice with STZ (50 mg/kg b/w for five consecutive days); insulin (1 U/day) was injected subcutaneously for ten consecutive days before the induction of diabetes and for a further ten days. Seventy-one male C57B16/J mite were grouped as follows: Group I (n = 25) made diabetic with i,p, STZ, Group 2 (n = 21) made diabetic with i,p, STZ and injected subcutaneously with insulin, Group 3 (It = 15) injected with insulin, while Group 4 (n = 10) comprised normal animals as controls. The animals of each group were killed at two intervals: half of them at day 12 and the remainder at day 24 from the beginning of the STZ treatment. A significant reduction of glycemia levels and insulitis severity was observed between mice of Group 1 vs. Group 2 at day 12 and day 24, Down-regulation of islet antigen expression (insulin, A2B5, GM2-1, ICA Ag) was achieved even without a complete metabolic suppression of beta-cell activity. In conclusion, prophylactic insulin treatment is effective to reduce glycemia levels and insulitis severity and down-regulates islet antigen expression in the LD-STZ model

    IA-2 combined epitope assay: a new, highly sensitive approach to evaluate IA-2 humoral autoimmunity in type 1 diabetes

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    Islet tyrosine phosphatase 2 (IA-2) is one of the major autoantigens in type 1 diabetes. The aim of this work was to evaluate which IA-2 construct(s) among those usually employed has the highest sensitivity and specificity for detecting IA-2 autoantibodies in autoimmune diabetes and whether the combination of different IA-2 constructs into a single assay allows the detection of immunoreactivities otherwise not detectable by a single construct. For this purpose, we tested the single immunoreactivities of IA-2(FL)(aa 1-979), IA-2(BDC)(aa 256-556:630979), IA-2(IC)(aa 605-979), IA-2(aa 256-760), IA-2(aa 761-928), and of 7 combinations of these fragments in the sera of 203 newly diagnosed type 1 diabetic patient (DM: 109 males,94 females, mean age 12.9 +/- 7.5 years) and 43 prediabetic subject (PDM: 20 males, 23 females, mean age 10.3 +/- 6.0 years) sera. IA-2(IC) was the single construct that showed the highest sensitivity and specificity both in DM and PDM subjects, however, all of the other IA-2 constructs investigated detected additional immunoreactivities with respect to it. The combined use into the same assay of IA-2(IC), IA-2(FL), and IA-2((256-760)) constructs allowed detection of IA-2 Abs in additional 13.3% DM and 30.4% PDM subjects compared to the single IA-2(IC) construct, suggesting this methodology as a new, highly sensitive approach to the study of IA-2 autoimmunity in type 1 diabetes. (c) 2005 Elsevier Inc. All rights reserved
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