Publications (24) View all
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Article: Serum IgE reactivity profiling in an asthma affected cohort.
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ABSTRACT: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.PLoS ONE 01/2011; 6(8):e22319. · 4.09 Impact Factor -
Article: [Heterozonal electrocardiographic changes in ST-elevation myocardial infarction].
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ABSTRACT: It has been observed that in patients with ST-elevation myocardial infarction (STEMI) the presence of ST-segment depression (ST) in heterozonal electrocardiographic leads (remote STI) worsens the patient's prognosis. The aim of this study was to observe in an unselected population with a first STEMI the incidence of remote STI and the risk factors related to this condition. We evaluated retrospectively 350 patients with a first STEMI; we excluded from our analysis 139 patients because no data about their coronary anatomy was available. ST-segment depression in the heterozonal myocardium was considered significant if > 0.1 mV at 60 ms from the J point, in at least two electrocardiographic leads. Patients were classified according to the presence (group 1, 117 patients) or absence (group II, 94 patients) of remote ST. The two groups did not differ for age, sex and coronary anatomy. In group I we found more heterozonal wall motion abnormalities than group II (32 vs. 18%, p = 0.018). In this group there was a higher incidence of smokers (56 vs. 33%, p = 0.025) and less patients were treated with statins when the STEMI occurred (6 vs. 14%, p = 0.047). Patients with remote ST had higher total cholesterol (214.6 +/- 48.9 vs. 192.3 +/- 29.8 mg/dl, p < 0.001) and low-density lipoprotein cholesterol (138.7 +/- 40.7 vs. 123.2 +/- 22.9 mg/dl, p < 0.0001) levels. Conclusions. In patients with STEMI the presence of remote ST is rather frequent, and seems to indicate a real heterozonal ischemia, independently of an epicardial coronary stenosis of the non-infarct-related artery. Remote ST. is associated with a higher incidence of risk factors related to microcirculatory dysfunction, such as cigarette smoking, a worse lipid profile and less protective factors, such as the use of statins prior to acute myocardial infarction.Giornale italiano di cardiologia (2006) 02/2007; 8(2):115-22. -
Article: Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study.
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ABSTRACT: This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study. IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects. IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56). The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.The American Journal of Gastroenterology 09/2004; 99(8):1551-6. · 7.28 Impact Factor -
Article: Immune reaction against the cytoskeleton in coeliac disease.
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ABSTRACT: The cytoskeleton actin network of intestinal microvilli has been found to be rapidly impaired after gluten challenge in coeliac disease (CD). The aim of this study was to investigate the presence of an immune reaction towards cytoskeleton structures such as actin filaments in CD. Eighty three antiendomysial antibody positive CD patients (52 children and 31 adults) were studied at our outpatient clinics from 1996 to 1998 using indirect immunofluorescence, ELISA, and western blotting for antiactin (AAA) and antitissue transglutaminase (TGA) antibodies before and after a gluten free diet (GFD). Sixteen patients with smooth muscle antibody positive autoimmune hepatitis, 21 with inflammatory bowel diseases, seven with small bowel bacterial overgrowth, and 60 healthy subjects were studied as controls. Fifty nine of 83 CD patients (28/31 adults (90.3%); 31/52 children (59.6%)) were positive for IgA and/or IgG AAA. Seventy seven (92.7%) were positive for IgA TGA. IgA AAA were strongly correlated with more severe degrees of intestinal villous atrophy (p<0.0001; relative risk 86.17). After a GFD, AAA became undetectable within five months. Apart from the immune reaction against the extracellular matrix, we have described an immune reaction against the cytoskeleton in both children and adults with CD. As AAA are strongly associated with more severe degrees of villous atrophy, they may represent a useful serological marker of severe intestinal atrophy in CD.Gut 10/2000; 47(4):520-6. · 10.11 Impact Factor -
Article: Myocilin Gln368stop mutation and advanced age as risk factors for late-onset primary open-angle glaucoma.
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ABSTRACT: Juvenile open-angle glaucoma has been found to be associated with molecular defects in the myocilin (MYOC) gene. Most of the defects are missense mutations located in the third exon. The Gln368stop mutation has recently been found in several cases of late-onset primary open-angle glaucoma (POAG). To study the effect of glaucoma risk in a relatively homogeneous genetic population. A clinical study was performed in all living members of a 5-generation family. DNA analysis was performed for studying association with genetic markers and identifying the mutation. We identified the Gln368stop molecular defect in 19 patients with POAG, 5 patients with ocular hypertension, and 22 healthy carriers. We compared affected and unaffected carriers based on age at onset and last examination, respectively. Besides the presence of 3 young patients with POAG (<40 years old), the number of glaucomatous patients in the advanced age group increased. The penetrance of glaucoma increases with age in Gln368stop carriers, but some remain unaffected at advanced age and others are affected at an early age. This suggests that additional risk factors are operating within this family, which may be identified by a genome-wide linkage search in this large pedigree. The myocilin Gln368stop mutation shows a good genotype-phenotype correlation and should be investigated in all familiar cases of chronic POAG. This may be important for early diagnosis and periodical checkups of presymptomatic individuals belonging to these families.Archives of Ophthalmology 06/2000; 118(5):674-9. · 3.71 Impact Factor
