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M Fusconi

Publications and source records attributed to M Fusconi.

At least 19 recordsLinked to original sources

Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?

BACKGROUND: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored. OBJECTIVES: To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases). METHODS: Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control). RESULTS: The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87-93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42-50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples. CONCLUSIONS: In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.

Adolescent↗

Anti-cyclic citrullinated peptide antibodies in type 1 autoimmune hepatitis.

BACKGROUND: Besides the autoantibodies included in the diagnostic criteria of type 1 autoimmune hepatitis, many other autoantibodies have been described in this condition. Recently, antibodies against cyclic citrullinated peptide have been validated as specific diagnostic and prognostic markers of rheumatoid arthritis. AIM: To assess whether these antibodies are part of the autoantibody repertoire of type 1 autoimmune hepatitis and correlate with rheumatological manifestations. METHODS: Antibodies against cyclic citrullinated peptide were tested by a commercially available enzyme-linked immunosorbent assay. RESULTS: The antibodies were found in 12 of 133 (9%) type 1 autoimmune hepatitis, two of 49 (4%) with primary biliary cirrhosis, one of 80 (1%) with hepatitis C virus-related chronic liver disease and 53 of 89 (60%) with rheumatoid arthritis serum samples. High titres were found only in rheumatoid arthritis and type 1 autoimmune hepatitis. No clinical (in particular rheumatological manifestations), biochemical or immunoserological differences were detectable between antibodies against cyclic citrullinated peptide positive and negative type 1 autoimmune hepatitis sera, with the exception of rheumatoid factor, always negative in the positive ones. CONCLUSIONS: Antibodies against cyclic citrullinated peptide can be detected in a subgroup of patients with type 1 autoimmune hepatitis. They might be part of the wide range of autoantibody production characteristic of this condition and/or, less probably, be predictive of future rheumatoid arthritis development.

Adolescent↗

Bile duct cell apoptosis is a rare event in primary biliary cirrhosis.

BACKGROUND: The frequency of apoptosis in bile duct cells of primary biliary cirrhosis is still unclear spanning from rare to 50% in the various reports. AIM: To study bile duct cell apoptosis in stage I primary biliary cirrhosis lesions. PATIENTS: Nine stage I-II biopsies with a total number of 26 bile ducts of different sizes, selected from a larger series on the basis of the expression on serial frozen sections of HLA-DR and Fas antigens. METHODS: Apoptosis was evaluated by a DNA fragmentation assay on frozen sections, according to the manufacturer's protocol and by expression of apoptosis related cytokeratin neoepitopes. Bile duct cell proliferation was assessed by MIB1 (Ki-67) expression. RESULTS: Apoptosis was frequently found in inflammatory cells of portal tracts and sinusoids. Apoptosis of hepatocytes was also systematically observed. Only 4 positive bile duct cells were found in 3 bile ducts from 3 biopsies. Quantitative evaluation was not attempted. Cholangiocyte proliferation was observed in the same ducts and occasionally in other biopsies. CONCLUSIONS: These data suggest that cholangiocyte death by apoptosis at the level of typical primary biliary cirrhosis lesions is a rare event, at least in early stages of the disease. The observed rate of proliferation was consistent with the rate of apoptosis.

Adult↗

Anti-CagA reactivity in Helicobacter pylori-negative subjects: a comparison of three different methods.

Emerging evidence suggests that infection by CagA-positive Helicobacter pylori strains is related to the development of more serious gastroduodenal diseases, thus conferring to the determination of anti-CagA antibodies a relevant clinical significance in serological screenings. The detection of anti-CagA positivity in sera negative for anti-H. pylori antibodies raises the question of whether this apparently nonsense result is merely due to a false positive reaction. To address this issue, we compared three different methods for the detection of anti-CagA antibodies. In all, 272 selected sera from patients with precisely defined H. pylori status (positive or negative concordance of five tests, ie, histology by Giemsa in both antrum and corpus, rapid urease test, culture, [13C]urea breath test, IgG ELISA) were tested for anti-CagA reactivity by three different techniques (western immunoblotting, ELISA, and recombinant immunoblotting assay). In order to assess the sensibility and specificity of each tests, we considered as "true" anti-CagA positive sera those with two out of three positive results. Sera from 70% of H. pylori-positive patients and 10% from H. pylori-negative patients turned out to be "true" positives for anti-CagA antibodies. The three methods showed similar excellent results, in terms of both sensitivity and specificity, always over 93%. It is confirmed that a proportion of patients with a negative conventional serology against H. pylori possess anti-CagA antibodies in their sera. In this paper we demonstrate that it can happen even in patients without any biological signs of actual H. pylori infection. The possibility that this can be due to a false positive laboratory result is very likely ruled out by the accuracy of the three methods used. The clinical management of these patients needs further study on larger series.

Adult↗

Cerebrospinal fluid leak management following cerebellopontine angle surgery.

OBJECTIVE: Postoperative cerebrospinal fluid leak (CSF) is a serious complication of the cerebellopontine angle surgery. In the current literature, CSF leak rates vary from 8.1 to 20%. The various options in managing this troublesome complication include conservative treatment or invasive surgical repair. The focus of this report is to retrospectively analyze our experience on this specific topic reviewing the incidence of CSF leak and the outcomes of its treatment in a group of patients who underwent surgery for different pathology of the cerebellopontine angle. METHOD: Eighty-five patients who underwent primary surgical procedures performed by a single neurologist were selected for this study. There were 70 surgical removals of acoustic neuromas, and 15 other cerebellopontine lesions. RESULTS: The overall incidence of CSF leak in the total group analyzed was 17.6%. There were five CSF rhinorrheas and 10 wound CSF leaks. Ten acoustic neuromas and five other cerebellopontine angle lesions exhibited this complication. The leak was cured in 53.3% of the cases using a continuous lumbar cerebrospinal fluid drainage (CLCFD). In two patients, the leak was treated with an extradural repair. CONCLUSIONS: Although CLCFD is not routinely used in the treatment of the CSF leak, it proved to be an efficacious and safe option, confirmed by no meningitis observed in our patients treated with this method.

Adult↗

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↗

Serum autoantibodies and the diagnosis of type-1 autoimmune hepatitis in Italy: a reappraisal at the light of hepatitis C virus infection.

Antinuclear antibodies with the homogeneous pattern (ANA-H) and smooth muscle antibodies with antiactin specificity (SMA-AA) are regarded as the serum markers of type-1 autoimmune chronic hepatitis. Their diagnostic relevance, however, has been questioned recently after the detection of signs of hepatitis C virus infection in autoimmune chronic hepatitis patients. To further evaluate this point, antihepatitis C virus antibodies were sought by two second generation assays (ELISA 2 and RIBA 2) in 100 Italian patients with chronic liver disease of unknown aetiology, including 46 with (autoimmune chronic hepatitis) and 54 without the above antibodies (cryptogenic). By ELISA 2, antihepatitis C virus, although significantly prevalent in cryptogenic (83%), were found also in a substantial proportion of autoimmune chronic hepatitis patients (46%) (p < 0.0001), their occurrence was confirmed by RIBA 2 in almost all cases (96% and 86%, respectively). Autoimmune patients with either ANA-H or SMA-AA exhibited similar antihepatitis C virus prevalences (59% and 52%, respectively); by contrast, the eight cases positive for both the autoantibodies were consistently antihepatitis C virus negative. These findings confirm that in countries with high hepatitis C virus circulation (like Italy) an overlap between autoimmune chronic hepatitis and hepatitis C virus infection, reflected by 'true' antihepatitis C virus antibodies, does occur. The detection of ANA-H or SMA-AA, in fact, identifies chronic liver disease patients with a relatively low prevalence of antihepatitis C virus, but does not exclude hepatitis C virus infection. Positive findings for both ANA-H and SMA-AA, however, is an appropriate marker for hepatitis C virus free 'primary' autoimmune chronic hepatitis.

Actins↗

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↗

Comparative efficacy of cefotetan and clindamycin plus amikacin as antimicrobial prophylaxis for major head and neck surgery.

A total of 41 patients were randomly allocated to receive either cefotetan (total dose, 20 g) or clindamycin (total dose, 12 g) plus amikacin (total dose, 5 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, male to female ratio, stage of cancer, and the various types of surgery. No patient received radiotherapy or chemotherapy before surgery. The wound infection rate was 4% in the group of patients receiving cefotetan and 0% in the group receiving clindamycin plus amikacin. No major side effects were observed in either group. On the basis of this study a five-day perioperative course with cefotetan may be considered effective antimicrobial prophylaxis in patients undergoing major head and neck oncologic surgery.

Amikacin↗

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↗