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Stocks of the WHO islet cell antibody, GAD65 antibody, and IA-2 antibody standard (NIBSC 97/550) are now very limited. We have therefore made and tested a series of control preparations in which human monoclonal autoantibodies to IA-2 and to GAD65 were diluted in antibody-negative human serum to different concentrations. Three different diabetes autoantibody controls (DAC 1–3) were made as was a negative control preparation. Aliquots containing 1 mL of autoantibodies in serum were freeze-dried. After reconstitution (with 1 mL of water) the controls were tested by 125I-IA-2 immunoprecipitation assay (IPA), 125I-GAD65 IPA, GAD65 Ab ELISA and IA-2 Ab ELISA (kits from RSR Ltd.) and for ICA by immunofluorescence test (IFT). DAC1 is particularly suitable as a control for the 125I IA-2 IPA; DAC2 is suitable for the 125I-GAD65 IPA, GAD65 Ab ELISA, and IA-2 Ab ELISA; and DAC3 is suitable for the ICA IFT. Freeze-dried preparations showed good stability at 37°C. Reconstituted liquid preparations were stable when stored at 4°C and at 37°C. Availability of an essentially unlimited supply of these reagents should be useful in establishing reproducible and comparable measurements of diabetes autoantibodies in different laboratories using different assays. [ABSTRACT FROM AUTHOR]

Background Several studies have suggested a link between coeliac disease and other autoimmune diseases. Aim To compare the presence of autoimmune disease in children with coeliac disease and in controls. Methods When coeliac disease was diagnosed, 267 children were evaluated for clinical autoimmune disease (with signs/symptoms), subclinical autoimmune disease (with autoantibodies and subclinical impairment of the target organ) or potential autoimmune disease (with autoantibodies only) and compared with 220 healthy controls. 170 coeliac disease patients were followed up for a mean 47 ± 31 months, in complete remission on a gluten-free diet. Ninety-nine controls were followed up for 45 ± 33 months. Results When coeliac disease was diagnosed, 71 (27%) children had autoimmune disease vs. 1% among the controls ( P < 0.001): 31 had clinical autoimmune disease and 40 had subclinical or potential autoimmune disease. During the follow-up, the clinical autoimmune disease cases slightly decreased from 12% to 11%, while the potential autoimmune disease cases increased from 14% to 21%. Of the 99 controls, none had any variation in their autoantibody profile. Conclusions Gluten-free diet does not modify the natural history of autoimmunity in patients with coeliac disease. However, gluten-free diet seems to produce a favourable effect on the previously present clinical autoimmune disease and to prevent the development of new clinical autoimmune disease, but does not affect the onset of potential autoimmunity, which tends to increase with time. [ABSTRACT FROM AUTHOR]

The aim was to estimate the prevalence of the serological markers of pancreatic autoimmunity in a cohort of Italian patients with type 1 diabetes mellitus occurring after 20 years of age in order to determine the prevalence of autoimmune diabetes and the most sensitive autoantibody combination to be employed for the diagnosis. We investigated 57 patients (31 males and 26 females) at clinical diagnosis of type 1 diabetes. 35 patients were 21–40 years and 22 were 41–72 years of age. Autoantibodies to islet-cells (ICA) were detected by indirect immunofluorescence, while those against glutamic acid decarboxylase (GADA), tyrosine-phosphatase (IA2A) and insulin (IAA) were detected by radiobinding assays. A positive test for at least one of the pancreatic autoantibodies was found in 45 of the 57 patients (78.9%). Coupling two antibody tests, GADA and/or IAA were found in 73.7%, ICA and/or GADA in 71.9%, while GADA and/or IA2A were found in 70.2% of the patients. The most frequently positive test was for GADA (66.7%). In general, the frequency of diabetes-related antibodies was higher in the 21–40-year-old group compared to the 41–72-year-old group and in females than males. Based on the detection of pancreatic autoantibodies determination, the great majority of the adult patients with recent onset type 1 diabetes were found to be autoimmune in nature. The best cost/benefit combination is provided by coupling the detection of GADA and ICA. [ABSTRACT FROM AUTHOR]

The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still under discussion and to assess the prevalence of thyroid autoantibodies and thyroid disease in the general population and to analyse the role of HCV in inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a small town in central Italy). Thyroid autoantibodies and nonorgan-specific autoantibodies (NOSAs) were tested in each subject, who were also screened for anti-HCV antibodies; all subjects found positive to HCV–RNA were considered as being HCV-infected. Thyroid function tests were performed in all subjects positive for thyroid autoantibody. Seventy-one subjects were found HCV-positive; four of these (5.6%) were positive for at least one thyroid autoantibody, as opposed to 7 (4.9%) of the 142 sex- and age-matched controls of the same population ( P = n.s.). Thyroid dysfunction was found in 2/4 HCV-positive, and in 1/7 HCV-negative subjects with thyroid autoantibodies ( P = n.s.). NOSAs were significantly more common in HCV-positive than in HCV-negative subjects ( P < 0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction, whereas HCV does seem to induce NOSAs. It should be taken into account, however, that the phenotypic expression of autoimmune diseases is obviously influenced by a number of risk factors, including genetic predisposition, female sex and infectious agents, that could trigger the onset of the disease. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-alpha (IFN-alpha).Research Design and Methods: The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.Results: None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment.Conclusions: We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease. [ABSTRACT FROM AUTHOR]

We studied 32 patients with idiopathic hypoparathyroidism (IHP), 19 patients with organ-specific autoimmune diseases (OSAD) without IHP, 50 normal controls and a known serum with anti-mitochondrial autoantibodies (AMA). Patients' sera were tested by the classical indirect immunofluorescent technique and by the indirect immunfluorescent complement fixation technique on unfixed cryostat sections of normal human parathyroid, pancreas, thyroid, stomach, kidney, and rat kidney. Five out of 32 patients with IHP, three out of 19 patients with OSAD without IHP and one out of 50 normal controls revealed a bright reactivity against oxyphil cells and a weak reactivity against chief cells of normal parathyroid. These sera also brightly reacted with mitochondria-rich cells and weakly with the remaining cells of only human tissues. The absorption of positive sera with human mitochondria completely abolished this positivity but the absorption with rat mitochondria failed to prevent this reaction. This reactivity was due to an antihuman mitochondrial autoantibody (AHMA) of IgG class. By non-competitive ELISA and Western blot we also demonstrated that every AHMA-positive serum mainly reacted against a human mitochondrial membrane-bound protein of approximate mol. wt. of 46 kd, while the AMA-positive serum reacted against different mitochondrial antigens. The present study shows that a specific parathyroid autoantibody was not detectable in patients with IHP. [ABSTRACT FROM AUTHOR]