Celiac disease in North Italian patients with autoimmune thyroid diseases.

BACKGROUND: Patients with autoimmune thyroid diseases (AITDs) are prone to develop other autoimmune manifestations and to display autoimmune polyendocrine syndromes. An increased prevalence of celiac disease (CD) was demonstrated in adult European and Italian patients with AITDs; conversely, an increased prevalence of AITDs was demonstrated in patients with CD. An IgA deficiency is the most frequent immunodeficiency in humans and, in general, high frequency of this disorder was demonstrated in those with autoimmune diseases. AIM: To define the prevalence of both CD and IgA deficiency in North Italian patients with AITDs. METHODS: 276 Italian patients with AITD were enrolled (mean age 42.6 years range 12-89, 186 of whom had chronic thyroiditis and 90 had Graves' disease). The tissue transglutaminase autoantibodies of the IgA class (IgA-tTGAbs) were evaluated using an ELISA method in these patients. Furthermore, the serological levels of the IgA were determined. RESULTS: Five of the patients (1.8%) were affected by previously diagnosed CD and were on a gluten-free diet. Ten out of the remaining 271 patients (3.6%) were found to be positive for celiac-related autoantibodies. All of these patients agreed to undergo endoscopy and duodenal biopsies and silent CD was found in 5 of them but 5 had not histopathological signs of CD. CD (clinical, silent or latent) was present in 15/276 (5.4%) of the North Italian patients with AITD; this prevalence is significantly higher with respect to the general population (p < 0.00001). The genetic pattern of the 10 patients with both AITDs and CD was characterized by the presence of DQ2 in 8 patients and DQ8 in 2. An IgA deficiency was present in 2/276 of the patients (0.72%). CONCLUSIONS: CD is significantly increased in patients with thyroid autoimmune disorders for this reason it is important to screen for CD in patients with AITDs.

Estimated risk for developing autoimmune Addison's disease in patients with adrenal cortex autoantibodies.

CONTEXT: Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison's disease (AAD) are at risk of adrenal failure. DESIGN: To assess the contribution of different clinical, immunological, genetic, and functional factors in the progression to AAD, we followed up 100 ACA-positive and 63 ACA-negative patients without AAD for a maximum of 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence and 21-OH autoantibodies (Abs) by RIA. Adrenal function was assessed by measuring basal levels of cortisol, aldosterone, ACTH, renin activity, and cortisol response to ACTH. The risk of developing AAD was calculated using survival and multivariate analyses. RESULTS: AAD developed in 31 ACA-positive patients and one ACA-negative patient. The cumulative risk of disease in ACA-positive patients was 48.5% [95% confidence interval (CI) 40.8-56.1]. The cumulative risk was higher in children than adults (100 vs. 31.9%; P < 0.0001), males than females (68.6 vs. 42.7%; P = 0.006), patients with subclinical rather than normal adrenal function at entry (87.4 vs. 30.1%; P < 0.0001), patients with hypoparathyroidism and/or candidiasis than patients with other autoimmune or nonautoimmune diseases (100 vs. 29.7%; P < 0.0001), and patients with high rather than low-medium ACA titers (62.8 vs. 41.2%; P = 0.12). The presence of human leukocyte antigen (HLA)-DRB1 did not appear to contribute to the prediction of AAD. Adjusted hazard ratios by Cox model for the development of AAD were 3.37 for males (CI 1.38-8.24), 5.23 for hypoparathyroidism and/or candidiasis (CI 1.53-17.92), 3.33 for high antibody titers (CI 1.43-7.78), and 6.15 for impaired adrenal function at entry (CI 2.79-13.57). CONCLUSIONS: These results were used to construct a risk algorithm for estimating the probability of developing AAD from the combination of gender, age, adrenal function, antibody titer, and associated autoimmune disorders at entry. The values of estimated risk could be used to decide appropriate follow-up intervals and future immunointervention strategies.

Celiac disease in North Italian patients with autoimmune Addison's disease.

OBJECTIVE: Patients with autoimmune Addison's disease (AAD) are prone to develop other autoimmune manifestations. An increased prevalence of celiac disease (CD) has recently been demonstrated in Northern European patients with AAD. IgA deficiency is the most frequent type of immunodeficiency among humans and is present in about one in every 600 individuals in the population. IgA deficiency is frequent in patients with other autoimmune diseases, but data concerning AAD are still unavailable. DESIGN: The aim was to define the prevalence of CD and of IgA deficiency in a group of Italian patients with AAD. METHODS: One hundred and nine patients with AAD were enrolled and examined for tissue transglutaminase autoantibodies of the IgA class, circulating levels of IgA and adrenal cortex antibodies. RESULTS: Two (1.8%) of the patients were affected by already diagnosed CD and were already on a gluten-free diet. Out of the remaining 107 patients, four (3.7%) were found to be positive for IgA antibodies to human tissue transglutaminase. Three of the four patients who were positive for tissue transglutaminase autoantibodies agreed to undergo endoscopy and duodenal biopsies and, in one, a latent form of CD was identified. The clinical, silent or latent form of CD was present in six out of 109 (5.4%). This prevalence was significantly higher (P = 0.0001) than that reported for the Northern Italian population which was equal to 0.063%. Specifically, CD was present in 12.5% of the autoimmune polyglandular syndrome (APS) type 1 cases, in four out of 60 (6.7%) of the APS type 2 cases and in one out of 40 (2.5%) of the isolated AAD cases. IgA deficiency was present in two out of 109 patients (1.8%), all of whom had normal IgG anti-gliadin. Autoantibodies to the adrenal cortex were detected in 81 out of 109 patients (74.3%). CONCLUSIONS: In patients with AAD there is a high prevalence of both CD and IgA deficiency. Consequently, it is important to screen for CD with tissue transglutaminase autoantibodies of the IgA class and for IgA levels.

Helicobacter pylori infection and gastric autoimmune diseases: is there a link?

BACKGROUND: Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. PATIENTS AND METHODS: We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody-negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B12, and circulating antibodies to H. pylori and to intrinsic factor were also determined. RESULTS: We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p =.01). Mean levels of gastrin were increased (p <.0001), while those of pepsinogen were reduced (p <.001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti-H. pylori antibodies were detected in 46 parietal cell antibody-positive subjects (58%) compared with 26 controls (39%) (p =.03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p <.001 vs. controls). Mean levels of gastrin were markedly increased (p <.0001) and those of pepsinogen I decreased (p <.0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody-positive subjects (58%) (p =.003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p <.001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. CONCLUSIONS: The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.