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Aim: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. Data synthesis: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. Conclusions: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1stquartile ¼ 1.13, 95% CI: 1.02-1.24, Ptrend ¼ 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend ¼ 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile ¼ 1.22, 95% CI: 1.08-1.38, Ptrend ¼ 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion: These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Purpose: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. Materials and methods: Institutional review board approval was obtained, and patients’ consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. Results: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was −67 ± 19% vs. −57 ± 21% (p < 0.001) − 70 ± 19% vs. −62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (−69 ± 19 vs. −50 ± 21, p = 0.001) and (−73 ± 18 vs. −54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator’s skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator’s skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography-mass spectrometry (GC-MS) techniques coupled with direct immersion solid-phase micro-extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5-3 ng/mg), moderate (3.1-10 ng/mg) and heavy (10.1-40 ng/mg). The Substance Abuse and Mental Health Services Administration cut-off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22-3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22-1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption.

Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity.

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The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure.

Since levamisole has been increasingly found as a component of illicit drugs, a robust method to detect its presence in hair samples is needed. However, no systematic research on the detection of levamisole in hair samples has been published. The method presented here uses direct immersion solid-phase microextraction coupled with gas chromatography and mass spectrometry (DI-SPME-GC/MS) to detect levamisole and minor cocaine congeners in hair samples using a single-extraction method.

It may be advantageous to use sweat, rather than blood or urine, to monitor individuals' drug exposure for the purposes of drug treatment programs, employment initiatives, and forensic investigations. Forty-eight patients receiving methadone at the Public Service for the Treatment of Drug Dependence of Perugia (Italy) were monitored for 14 days by the analysis of methadone and cocaine present in two sweat patches, each worn for 7 days. The results were compared to those from the analysis of urine samples collected at the beginning of the study and after 7 days, as well as those from the analysis of hair collected on the fourteenth day. Sweat patch analysis was positive for methadone and its metabolite EDDP in 100% of patients. Some individuals were positive for cocaine in urine, sweat, and hair while others were positive for cocaine in only one of those samples. Results suggest analysis of a sweat patch indicates an individual's drug use or drug washout for the previous week, and provides an alternative to blood or urine analyses.

Peyote, a cactus containing the hallucinogen mescaline, is used to induce altered states of consciousness in religious ceremonies or for recreational purpose. This study reports a case of an underage boy suspected of mescaline abuse. For this purpose, we analyzed a dark green liquid sample found in the bedroom of the boy whose urine and hair samples were collected shortly after the drink was found. A method by gas chromatography-mass spectrometry tandem mass spectrometry (GC-MS/MS) in positive chemical ionization mode was developed and validated in terms of linearity, specificity, accuracy, and sensitivity for mescaline determination at the low concentrations present in hair. GC-MS analysis of the liquid identified mescaline, while urine was negative; GC-MS/MS segmental hair analysis identified mescaline in the proximal segment (root to 2 cm), while the distal segments were negative. Although peyote was uncommonly encountered, its use was confirmed by segmental hair analysis that can provide long-term information about drugs use.

A simple and sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) method is described for the detection of anabolic steroids, usually found in keratin matrix at very low concentrations. Hair samples from seven athletes who spontaneously reported their abuse of anabolic steroids, and in a single case cocaine, were analyzed for methyltestosterone, nandrolone, boldenone, fluoxymesterolone, cocaine and its metabolite benzoylecgonine. Anabolic steroids were determinate by digestion of hair samples in 1 m NaOH for 15 min at 95 degrees C. After cooling, samples were purificated by solid-phase and liquid-liquid extraction, then anabolic steroids were converted to their trimethylsilyl derivative and finally analyzed by GC/MS/MS. For detection of cocaine and benzoylecgonine, hair samples were extracted with methanol in an ultrasonic bath for 2 h at 56 degrees C then overnight in a thermostatic bath at the same temperature. After the incubation, methanol was evaporated to dryness, and benzoylecgonine was converted to its trimethylsilyl derivative prior of GC/MS/MS analysis. Results obtained are in agreement with the athletes' reports, confirming that hair is a valid biological matrix to establish long-term intake of drugs.

CONTEXT: The polymorphism of class II HLA genes modulates the genetic risk for several endocrine autoimmune diseases. The constitutive class II expression on antigen-presenting cells is under the control of the MHC class II transactivator, encoded by the MHC2TA gene, which is mapped to chromosome 16p13. The MHC2TA -168 A-->G single nucleotide polymorphism (rs3087456) has been suggested to confer susceptibility to some autoimmune diseases. DESIGN: With the aim of testing whether this MHC2TA single nucleotide polymorphism is independently associated with autoimmune Addison's disease (AAD) and/or modulates the genetic risk conferred by DRB1-DQA1-DQB1 haplotypes, we analyzed DNA samples from 128 AAD patients and 406 healthy control subjects from continental Italy. RESULTS: Frequency of allele G of MHC2TA was significantly increased among AAD patients (39% alleles), compared with 29% in healthy controls (P = 0.003). Similarly, the frequency of AG+GG genotypes was significantly higher among AAD patients than among healthy control subjects, in both a codominant (P = 0.012) and a G-dominant model (P = 0.018). Multivariate logistic regression analysis showed that MHC2TA AG+GG continued to be positively associated with genetic risk for AAD (P = 0.028, odds ratio = 1.72, 95% confidence interval = 1.06-2.78), after correction for DRB1*03-DQA1*0501-DQB1*0201, DRB1*04 (not 0403)-DQA1*0301-DQB1*0302 and DRB1*0403. Similar results were obtained when the number of G alleles was included in the model (P = 0.004; odds ratio = 1.65, 95% confidence interval = 1.17-2.32). CONCLUSIONS: Our study provides the first demonstration of the association of the polymorphism of the MHC2TA gene with genetic risk for AAD that appears to be independent from the well-known association with the polymorphism of HLA class II genes.

Because of its peculiar characteristics, hair analysis provides a way of obtaining information that cannot be acquired by other commonly used forensic medical analyses, such as blood or urine analysis. In the keratin matrix many xenobiotics are incorporated permanently, in contrast to the situation with blood or urine where they are generally only detectable for a few hours or days. Therefore hair analysis should be the method of choice in the clinical and forensic toxicology field when the assessment of repeated or chronic exposure to a drug is required, e.g. in the case of criminal responsibility, revocation/restoration of a driving licence or in workplace testing. Some factors that can affect the concentrations of drugs in hair, such as passive contamination, age, ethnicity and cosmetic treatment, must be considered. Analytical methodology is also very important: GC/MS/MS has proved to be a highly sensitive and specific technique for the detection of very low concentrations of such drugs in hair. In this study five cases of the application of hair analyses using this technique for the determination of abused drugs (opiates, cocaine, amphetamine, anabolic steroids) are described.

The attraction of leukocytes to tissues is essential for inflammation and the initiation of the autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytokines. We investigated whether human chemokine receptor gene polymorphisms, namely CCR5-Delta32 and CCR2-64I, are associated with susceptibility to autoimmune Addison's disease. Genotyping was performed in 56 patients and 127 healthy controls by a new method using pyrosequencing for CCR2-64I and by polymerase chain reaction and detecting gel for CCR5-Delta32. None of the CCR2 or CCR5 alleles was found to be associated, either positively or negatively, with disease risk. Our results indicate that the CCR2-64I and CCR5-Delta32 gene polymorphisms do not play a major role in conferring genetic risk for, and/or protection against, autoimmune Addison's disease., QC 20100525 QC 20111028

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

It is well known that type I diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-Delta32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-Delta32 gene polymorphism and TIDM and we desrcibe a new method for a simple and more precise genotyping of the CCR2 gene., QC 20100525

The equilibrium of sexual hormones in both sexes is controlled in vertebrates by the enzyme aromatase, a member of the cytochrome P450 superfamily, which catalyzes the conversion of androstenedione and testosterone into estrone and estradiol, respectively. Flavonoids are diphenolic compounds present in whole grains, legumes, fruits, and vegetables that are strongly implicated as protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin, found in high concentrations in honey and propolis, has been shown to be an inhibitor of aromatase enzyme activity. These foods are often used as supplements, particulary by sportsmen for their energetic and antioxidant properties. The aim of this study was to verify if daily treatment for 21 days with propolis and honey, containing chrysin, would modify urinary concentrations of testosterone in volunteer male subjects. In fact, aromatase inhibition by chrysin could block the conversion of androgens into estrogens with a consequent increase of testosterone, eventually measurable in urine samples. The obtained data did not show alterations of the levels of testosterone in the volunteers after 7, 14, and 21 days of treatment in comparison with baseline values and compared with measurements on the control subjects at the same time. In conclusion, the use of these foods for 21 days at the doses usually taken as oral supplementation does not have effects on the equilibrium of testosterone in human males.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by Tlymphocyte infiltration of islets of Langerhans with consequent destruction of beta cells. A permissive genetic background is required for the development of the islet autoimmune process. The strongest genetic association identified is that with HLA class II genes located on the short arm of chromosome 6. It is well known that both HLA DRB1*04-DQA1*0301DQB1*0302 (DR4-DQ8) and DRB1*03DQA1*0501-DQB1*0201 (DR3-DQ2) are positively, and DRB1*15-DQA1*0102-DQB1*0602 is negatively, associated with T1DM. However, only a minority of die subjects carrying the high-risk haplotypes/genotypes develops the disease, which suggests that additional genes play a crucial role in conferring either protection or susceptibility to T1DM. The heterogeneity of the clinical and immunological features of T1 DM in relation to age at clinical onset is a complicating factor. In our project we identified, by first, LADA patients among subjects with clinical diagnosis of type 2 diabetes. The presence of GAD65Ab, but not that of IA2/ICA512Ab, identified a large subgroup of autoimmune diabetic subjects, initially classified as having type 2 diabetes, with an increased risk for thyroid and adrenal autoimmunity and increased frequency of the haplotype HLA-DR3/DQ2. With the aim of increasing the diagnostic specificity of GAD65Ab, we studied the selection of GAD65 antibody epitopes. Autoantibodies directed to the COOH-terminal end of GAD65 (GAD65CAb) were more frequent in insulin treated subjects, while the exclusive presence of autoantibodies to the middle region of the autoantigen (GAD65-MAb) was more frequent in subjects treated with hypoglycaemic agents and/or diet The diagnostic specificity for insulin requirement increased from 96.9% of the typical GAD65Ab assay to 99.4% of GAD65-CAb. Recently, a distinct family of MHC genes has been identified within the class III region and has been denominated MHC class I chain-related ge