Maria Paola Musu

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (12)103.47 Total impact

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    ABSTRACT: AIM: An option to reduce the number of duodenal biopsies in the diagnosis of coeliac disease (CD) has recently been reported by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. New criteria showed that the duodenal biopsy may be avoided in presence of symptoms, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysial antibodies (EMA) and at-risk HLA, whilst biopsy still remains mandatory for individuals with moderate and low anti-TG2 levels. In this study, we considered the addition of serum measurement of anti-actin IgA antibody (AAA-IgA) to the new criteria, with the aim of further reducing the number of duodenal biopsies. METHODS: One hundred and forty consecutive symptomatic CD children and 78 controls were studied. All subjects were classified according to the new criteria with the addition of AAA-IgA levels and results were compared with the outcome of duodenal biopsy. RESULTS: The biopsies from the sixty-four individuals (out of 218) identified by the new criteria, presence of symptoms, anti-TG2 levels >10 times upper limit of normal (ULN), positive EMA and at-risk HLA, showed CD with a Marsh 3 lesion. In the remaining individuals, the addition of AAA-IgA allowed the detection of further 20 CD patients with a Marsh 3 damage when moderate (4 to 10 times ULN) but not low anti-TG2 levels were present. CONCLUSIONS: Our study confirms that the new criteria may avoid the duodenal biopsy in many CD patients. Moreover, although our finding needs to be confirmed, positivity for AAA-IgA may further reduce the number of duodenal biopsies in moderate anti-TG2 levels.
    Journal of Gastroenterology and Hepatology Research 05/2013; 2(5).
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    Maria Paola Musu ·
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    ABSTRACT: La celiachia (CD) è un’ enteropatia autoimmune causata dall’ingestione di alcuni cereali contenenti glutine, quali grano, orzo e segale, che colpisce soggetti geneticamente predisposti ed è caratterizzata da una alta variabilità delle manifestazioni cliniche e delle lesioni istologiche della mucosa duodenale. Le attuali metodiche sierologiche consentono solamente di avere un sospetto diagnostico di malattia celiaca e costituiscono l’indicazione ad eseguire una biopsia intestinale per una conferma diagnostica definitiva. Abbiamo così cercato di disporre di un marcatore sierologico di lesione intestinale da glutine offrendo così la possibilità di evitare un esame invasivo strumentale come la biopsia intestinale e di ridurre gli errori diagnostici legati alle difficoltà che possono esserci nella interpretazione delle lesioni istologiche. Così abbiamo effettuato un primo studio in cui dimostravamo la presenza di anticorpi serici anti-F actina (AAA-IgA) nella celiachia. Questa positività risulta correlata con la presenza di atrofia dei villi intestinali in pazienti affetti da malattia celiaca. Abbiamo così continuato includendo nel nostro studio un numero maggiore di pazienti celiaci per rendere ancora più veritiera la presenza di questi anticorpi e modificando la metodica per aumentare la sensibilità in quanto nel primo studio circa il 20% dei pazienti venivano perduti. Per questo abbiamo condotto uno studio in doppio cieco che ha coinvolto nove centri italiani di gastroenterologia (sei dei quali pediatrici) e un centro americano (Centro di Ricerca per la Malattia Celiaca di Baltimora, Maryland USA).

  • Journal of Pediatric Gastroenterology and Nutrition 10/2006; 43(4). DOI:10.1097/00005176-200610000-00029 · 2.63 Impact Factor
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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. DOI:10.1111/j.1572-0241.2004.30296.x · 10.76 Impact Factor

  • Journal of Pediatric Gastroenterology and Nutrition 06/2004; 39(Supplement 1). DOI:10.1097/00005176-200406001-00129 · 2.63 Impact Factor
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    ABSTRACT: The American Journal of Gastroenterology (2003) 98, S228; doi:10.1111/j.1572-0241.2003.08429.x
    The American Journal of Gastroenterology 09/2003; 98(9). DOI:10.1016/S0002-9270(03)01462-X · 10.76 Impact Factor

  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)83343-7 · 16.72 Impact Factor
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    ABSTRACT: Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.
    Gut 03/2003; 52(2):218-23. · 14.66 Impact Factor
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    ABSTRACT: Tissue transglutaminase enzyme-linked immunosorbent assay (tTG-ELISA) has recently been proposed as a simple and fast screening test for celiac disease (CD). The rate of false-positive and false-negative tests with tTG-ELISA, however, has not been definitively established. Therefore, the aim of our study was to investigate anti-tTG antibodies (TGA) not only in untreated patients with CD and in healthy controls, but also in a large group of patients with other autoimmune diseases. The presence of TGA was investigated in sera from 111 patients with untreated CD, 96 patients with other autoimmune conditions (28 with autoimmune liver disease, 46 with insulin-dependent diabetes mellitus, 10 with inflammatory bowel syndrome, 12 with type 1 polyglandular syndrome) and from 100 healthy controls using guinea pig tTG-ELISA (gp-TG/ELISA) and highly purified recombinant human tTG-ELISA (h-TG/ELISA). Western blotting with guinea pig tTG was also performed. Ninety-four patients with CD who tested positive for antiendomysial antibodies (AEA) and one who tested negative for AEA showed antibodies against the gp-TG. Among the controls, 50% of patients with autoimmune liver disease and 6.5% of patients with insulin-dependent diabetes mellitus tested positive with gp-TG/ELISA. Western blotting experiments revealed that the high rate of positive tests observed using ELISA among the control group sera is attributable to impurities in the gp-TG preparation. However, h-TG/ELISA tests were positive for the sera from all patients who tested positive for AEA and from one control who tested negative for AEA, whereas h-TG/ELISA tests were negative for all CD patients who tested negative for AEA and for other controls who tested negative for AEA. The frequency of false-negative and false-positive tests represents the major limit to the use of gp-tTG/ELISA. However, because h-TG/ELISA is both simple and fast, it could be used in large screening programs for CD.
    Journal of Pediatric Gastroenterology and Nutrition 02/2002; 34(1):31-4. DOI:10.1097/00005176-200201000-00008 · 2.63 Impact Factor

  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(08)81061-X · 16.72 Impact Factor

  • Journal of Hepatology 04/2001; 34:45. DOI:10.1016/S0168-8278(01)81023-0 · 11.34 Impact Factor
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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. · 14.66 Impact Factor