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F B Bianchi

Publications and source records attributed to F B Bianchi.

At least 19 recordsLinked to original sources

Gliadin immune reactivity is associated with overt and latent enteropathy in relatives of celiac patients.

Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.

Adolescent

Demonstration of peptide-specific and cross-reactive epitopes in proteins reacting with antimitochondrial antibodies of primary biliary cirrhosis.

Recently the main targets of antimitochondrial antibodies (AMA) of primary biliary cirrhosis have been identified as parts of three related mitochondrial multienzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain alpha-ketoacid dehydrogenase (BKDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH). Usually AMA-positive PBC serum samples show reactivity to more than one of these, raising the question whether they are exclusively different antibodies or are, at least in part, the result of cross-reactive specificities. With Western immunoblotting, four antigens with molecular masses of 74, 52, 51 and 43 kDa, are recognized by PBC sera. In this study, using affinity purified antibodies from mitochondrial proteins immobilized on nitrocellulose blots, we demonstrate the presence of peptide-specific and cross-reactive epitopes in some targets. In particular, at least three different epitopes present in the 74-kDa protein (presumed to by PDH-E2) are also present in the 51-kDa protein (probably PDH-X), and two in the 52-kDa peptide (possibly BCKDH-E2). Moreover, the 43-kDa mitochondrial protein (the identity of which is more problematic) has three epitopes. One of these is also present in the 74-, 52- and 51-kDa proteins, a second in the 74- and 51-kDa, and a third seems to be peptide-specific. These results show that different sera with the same immunoblotting pattern of reactivity can have antibodies with different antigenic specificities and, conversely, that the same specificity can be responsible for more than one band.

Adult

Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis.

Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten-free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect.

Adult

Antibodies to hepatitis C virus in autoimmune liver disease: evidence for geographical heterogeneity.

To resolve conflicting reports about the occurrence of antibodies against hepatitis C virus (HCV) in patients with autoimmune chronic active hepatitis (AI-CAH), sera from UK and Italian patients were tested with the original anti-HCV assay (Ortho) and a novel anti-HCV assay (UBI) based entirely on synthetic HCV peptides. 28 (60%) of 47 Italian patients with type-1 AI-CAH were anti-HCV-positive by Ortho ELISA, 25 of whom were also strongly positive by the UBI assay. 15 (60%) of 25 UK patients with type-1 AI-CAH were HCV-positive by Ortho ELISA but only 2 were positive by the UBI assay. Similarly, 29 (88%) of 33 Italian patients with type-2 AI-CAH, but 0 of 10 UK patients, were very strongly anti-HCV-positive with the UBI assay. Italian patients with AI-CAH appear to have a high frequency of genuine exposure to HCV, whereas seropositivity by the Ortho HCV ELISA in UK patients is likely to represent a false-positive result. These findings indicate important geographical and/or genetic influences in autoimmune liver disease among different populations.

Adult

Hepatitis C viraemia in adults with type 2 autoimmune hepatitis.

Sera from 14 patients with type 2 autoimmune hepatitis (anti-LKM1 positive) were investigated for evidence of hepatitis C virus (HCV) infection. Antibodies to HCV were detected in 13 patients by both commercial and "in-house" ELISAs and also by a second generation recombinant immunoblot assay. Nine of the 13 (69%) anti-HCV positive patients were shown to be viraemic by a polymerase chain reaction-based assay for serum HCV RNA. Neither anti-HCV nor serum HCV RNA were detected in any of 6 controls with primary biliary cirrhosis or in 39 healthy blood donors. These findings strongly suggest a role for HCV in the pathogenesis of type 2 autoimmune hepatitis.

Adolescent

IgA antiendomysial antibody test. A step forward in celiac disease screening.

Serum IgA antiendomysial antibodies (EmA) were found in 61 (87%) of 70 adults and children with untreated celiac disease, whereas IgA antigliadin antibodies (AGA) and IgA R1-antireticulin antibodies (R1-ARA) were positive in 71% and 47%, respectively, of the same patients. Two of the nine untreated celiacs negative for IgA EmA showed positivity for IgA AGA. While IgA AGA and R1-ARA disappeared in all the celiacs tested one year after gluten-free diet, IgA EmA persisted at low titer in seven (18%) of these 38 subjects, although the jejunal biopsy showed a complete regrowth of jejunal villi. All the disease control patients as well as the blood donors tested were always negative for the three IgA antibodies. Our results state that the search for both IgA EmA and AGA gives the best results in the screening of celiac disease, since the positivity for at least one of these two antibodies allows identification with a 100% specificity of the 90% of untreated celiac patients.

Adult

Anti-nuclear antibodies of primary biliary cirrhosis recognize 78-92-kD and 96-100-kD proteins of nuclear bodies.

The specificities of anti-nuclear antibodies (ANA) reacting with multiple nuclear dots (MND-ANA) present in about 15% primary biliary cirrhosis sera were studied by Western blot analysis with nuclear fractions from a human cell line. Reactivity with two broad bands of 78-92 kD and 96-100 kD of the insoluble fraction was present exclusively in MND-ANA-positive sera. Antibodies eluted from these proteins specifically retained the immunofluorescence reactivity of MND-ANA. Immunomorphological analysis by a pre-embedding technique revealed that the antibody specifically binds to nuclear regions resembling in size and number nuclear bodies. Since these structures are absent in immature rate endometrial cell and can be induced by diethylstilbestrol, we tested MND-ANA by immunofluorescence on cryostat sections of uteri from hormone-treated and untreated immature rats. A strong reaction of nuclear dots was observed predominantly in endometrial cells of hormone treated rats. We thus conclude that MND-ANA present in primary biliary cirrhosis sera are directed against 78-92-kD and 96-100-kD nuclear proteins located in nuclear bodies.

Animals

Serum non-organ specific autoantibodies in human immunodeficiency virus 1 infection.

Serum samples from 66 seropositive subjects (56 with a history of intravenous drug abuse), including asymptomatic carriers and patients with persistent generalised lymphadenopathy (PGL), AIDS related complex (ARC), and AIDS, were tested by indirect immunofluorescence on rat tissue sections and HEp-2 cells for the presence of antibodies to nuclei, smooth muscle, intermediate filaments (anti-IMF) and microfilaments (anti-MF). Counterimmunoelectrophoresis was also used to detect antibodies to extractable nuclear antigens. Smooth muscle antibodies with the V pattern or antinuclear antibodies, mainly of the speckled type, or anti-IMF, occurred in 35 cases, being widely distributed in all groups. Such an autoantibody response resembles the "viral" autoimmunity described in various infectious diseases and in particular that of non-A, non-B post-transfusion hepatitis. Autoantibodies may be of some prognostic relevance, as the prevalence of smooth muscle antibodies V increased as the disease progressed (asymptomatic carriers 20%, those with PGL 29%, those with ARC 47%, and those with AIDS 63%. In the PGL group autoantibody positivity correlated with the presence of skin anergy. The fact that autoantibodies were more frequently detected in patients with circulating immune complexes suggests that these can contain autoantibodies and the corresponding autoantigens.

AIDS-Related Complex

Anti-actin antibodies: a new test for an old problem.

Smooth muscle antibodies with anti-actin specificity are commonly regarded as markers of autoimmune liver disease. However, there are interpretational problems because different techniques have been used for their identification and therefore the results are difficult to compare. The present paper reports the results of a new method for the identification of anti-actin antibodies (indirect immunofluorescence on cryostat sections of liver from rats chronically injected with phalloidin). The results have been compared with those obtained by four other techniques: demonstration by immunofluorescence of kidney peritubular reactivity (SMAT), of anti-microfilament antibodies (on HEp-2 cells and vinblastine-treated peripheral blood mononuclear cells) and counterimmunoelectrophoresis with purified muscle actin as antigen. The new method proved to be the most sensitive and specific. Furthermore, its reproducibility was found to be high, the interpretation easy and the cost low. The clinical significance of anti-actin antibodies in patients with chronic liver disease is also discussed.

Actins

Type 2 autoimmune hepatitis and hepatitis C virus infection.

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay in 46 patients seropositive for liver-kidney microsomal antibody (anti-LKM1), the marker of autoimmune hepatitis type 2. 43 had chronic hepatitis (with histological confirmation in 34) and 3 were seropositive for anti-LKM1 without clinical or biochemical evidence of liver damage. The overall prevalence of anti-HCV was 78.2% or 86.1% in patients with chronic hepatitis--a similar prevalence to that reported in patients with chronic non A, non B posttransfusion hepatitis. HCV infection may lead to altered expression of the hepatocellullar LKM1 target antigen, with loss of tolerance and appearance of anti-LKM1 in serum.

Animals

Modulation of extracellular matrix components during dimethylnitrosamine-induced cirrhosis.

Liver fibrosis was induced in rats after administration of dimethylnitrosamine (DMN) intraperitoneally three times a week for 3 weeks. Incomplete septa appeared after 7 days and evidence of nodulation of the parenchyma was observed after 21 days. Both distribution of extracellular matrix components (collagen type I, type III and type IV, laminin, fibronectin, heparan sulphate proteoglycan) and the distribution of desmin as a marker of lipocytes (Ito cells) and of iso-alpha-smooth muscle actin were studied with immunoperoxidase. Changes in the distribution of extracellular matrix components outlined both the formation of septa and the development of nodules with changes in the sinusoidal pattern evoking aspects of capillarization. The number of desmin-positive cells increased in DMN-treated animals, showing a prominent reaction in the fibrous septa. In the normal liver, lipocytes were positive for laminin and negative for actin, but septal and juxta-septal lipocytes were positive for both antigens, suggesting the presence of transitional cells with mixed immunoreactivity. This was confirmed by ultrastructural studies which showed typical intraseptal myofibroblasts and other elements exhibiting the structural features of both myofibroblasts and lipocytes.

Actins