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V Altrinetti

Publications and source records attributed to V Altrinetti.

4 recordsLinked to original sources

Different intrathyroid expression of intercellular adhesion molecule-1 (ICAM-1) in Hashimoto's thyroiditis and Graves' disease: analysis at mRNA level and association with B7.1 costimulatory molecule.

Cultured thyroid epithelial cells can be induced to express intercellular adhesion molecule-1 (ICAM-1, or CD54). However, constitutive follicular expression of ICAM-1 has been reported only in thyroid autoimmunity. We evaluated the expression of ICAM-1 mRNA and protein on thyroid tissue from different autoimmune thyroid diseases, and its relationship with other immunologically relevant surface markers, namely costimulatory molecules of B7 family. Thyroid tissue sections were obtained by surgically removed thyroid glands from 6 patients with Hashimoto's thyroiditis (HT), 6 with Graves' disease (GD) and 3 with multinodular nontoxic goiter. We used in situ hybridization to localize ICAM-1 mRNA, and immunohistochemical analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) method. We showed a clear hybridization pattern, localized in follicular cells, in sections of glands with HT. The hybridization pattern was far less pronounced in GD: no staining was apparent on follicular cells. These results were strictly consistent with those obtained by means of immunohistochemistry. Moreover, double-staining experiments demonstrated colocalization of ICAM-1 and B7.1 molecules in HT, whereas no B7.1 expression was observed in Graves' or in non-autoimmune thyroid diseases. These data agree with the hypothesis of distinct immunoregulatory phenomena and effector mechanisms in the 2 main autoimmune thyroid diseases.

Adult↗

Regulation of apoptosis in endocrine autoimmunity: insights from Hashimoto's thyroiditis and Graves' disease.

Dysregulation of apoptosis is associated with the pathogenesis of organ-specific autoimmune diseases, through altered target organ susceptibility. Apoptosis signaling pathways can be initiated through activation of death receptors such as Fas. A comparative analysis of the expression of Fas and FasL, the antiapoptotic molecule Bcl-2, and apoptosis in both thyrocytes and thyroid-infiltrating lymphocytes (TILs) from patients with either Graves' disease (GD) or Hashimoto's thyroiditis (HT) was performed. GD thyrocytes expressed less Fas than HT thyrocytes, whereas GD TILs had higher levels of Fas and FasL than HT TILs. GD thyrocytes expressed higher levels of Bcl-2 compared with HT thyrocytes. The opposite pattern was observed in GD (low Bcl-2) and HT (high Bcl-2) TILs. Consistently, thyrocyte apoptosis was marked in HT and poor in GD thyroids, and TIL apoptosis was marked in GD and poor in HT. Our findings suggest that in GD thyroid the regulation of Fas/FasL/Bcl-2 favors apoptosis of infiltrating lymphocytes. Moreover, the reduced levels of Fas/FasL and increased levels of Bcl-2 should favor thyrocyte survival and hypertrophy associated with stimulatory thyroid-stimulating hormone receptor antibodies. In contrast, the regulation of Fas/FasL/Bcl-2 expression in HT can promote thyrocyte apoptosis via homophylic Fas-FasL interactions, and a gradual reduction in thyrocyte numbers leading to hypothyroidism. Fas-mediated apoptosis may be a general mechanism of cell damage in destructive organ-specific autoimmunity.

Apoptosis↗

Comparison of ELISA for tissue transglutaminase autoantibodies with antiendomysium antibodies in pediatric and adult patients with celiac disease.

BACKGROUND: Tissue transglutaminase (t-TG) is the main autoantigen recognized by the endomysium antibodies (EMA) observed in patients with celiac disease (CD). The aim of the study was to assess an ELISA method for t-TG antibodies (t-TGA) with respect to EMA IF assay in pediatric and adult patients. METHODS: t-TGA were analyzed by ELISA in 220 sera samples: 82 patients with biopsy-proven untreated CD (23 adults and 59 children), 14 CD children on gluten-free diet, 18 asymptomatic relatives of CD patients, and 106 age-matched control patients with gluten-unrelated gastrointestinal diseases (58 adults and 48 children). Serum IgA EMA were tested on umbilical cord sections in all patients. RESULTS: The great majority (92.7%) of untreated CD patients (both adults and children) were t-TGA positive (values ranging from 20.1 to > 300 AU). None of the child control patients and only two out of 58 (3.4%) of the adults with unrelated gastrointestinal diseases had serum t-TGA positivity; two out of 18 first-degree relatives with biopsy-proved silent CD were t-TGA (as well as EMA) positive. Finally, two out of 14 CD children, assuming a gluten-free diet, had serum t-TGA (as well as EMA). A highly significant correlation (P < 0.001) was observed between t-TGA concentrations and EMA. t-TGA showed a sensitivity of 87% and 95%, a specificity of 97% and 100% for adults and children, respectively. CONCLUSION: The method is highly sensitive and specific in the diagnosis of CD and is promising as a tool for routine diagnostic use and population screening, especially in children.

Adolescent↗