G R Corazza

University of Pavia, Ticinum, Lombardy, Italy

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Publications (621)3546.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The short isoform of thymic stromal lymphopoietin (TSLP), a cytokine constitutively expressed by epithelial cells, is crucial in preserving immune tolerance in the gut. TSLP deficiency has been implicated in sustaining intestinal damage in Crohn's disease. We explored mucosal TSLP expression and function in refractory and uncomplicated coeliac disease (CD), a T-cell-mediated enteropathy induced by gluten in genetically susceptible individuals. TSLP isoforms-long and short-and receptors-TSLPR and interleukin (IL)-7Rα-were assessed by immunofluorescence, immunoblotting and qRT-PCR in the duodenum of untreated, treated, potential and refractory patients with CD. The ability of the serine protease furin or CD biopsy supernatants to cleave TSLP was evaluated by immunoblotting. The production of interferon (IFN)-γ and IL-8 by untreated CD biopsies cultured ex vivo with TSLP isoforms was also assessed. Mucosal TSLP, but not TSLPR and IL-7Rα, was reduced in untreated CD and refractory CD in comparison to treated CD, potential CD and controls. Transcripts of both TSLP isoforms were decreased in active CD mucosa. Furin, which was overexpressed in active CD biopsies, was able to cleave TSLP in vitro. Accordingly, refractory and untreated CD supernatants showed higher TSLP-degrading capacity in comparison to treated CD and control supernatants. In our ex vivo model, both TSLP isoforms significantly downregulated IFN-γ and IL-8 production by untreated CD biopsies. Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 09/2015; DOI:10.1136/gutjnl-2014-308876 · 14.66 Impact Factor
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    ABSTRACT: The association between olmesartan and an enteropathy histologically indistinguishable from untreated celiac disease has recently been described. However, pathogenetic mechanisms leading to villous atrophy, prevalence, natural history and genetic background of this condition have not yet been defined. We describe here two cases of olmesartan-associated enteropathy and discuss some aspects of the natural history of this condition. In both patients, an infectious episode seems to have triggered the severe malabsorption syndrome which led them to hospitalization. High titer positive antinuclear antibodies with homogeneous pattern were found. Our reports add to a growing body of evidence suggesting that olmesartan-associated enteropathy should be considered in the presence of villous atrophy and negative celiac serology and in the diagnostic algorithm of non-responsive celiac disease.
    Scandinavian Journal of Gastroenterology 08/2015; DOI:10.3109/00365521.2015.1074719 · 2.36 Impact Factor
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    ABSTRACT: Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e. respectively anti-parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation -increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance -abnormal regulatory T cell function- are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. Copyright © 2015. Published by Elsevier B.V.
    Autoimmunity reviews 08/2015; DOI:10.1016/j.autrev.2015.08.004 · 7.93 Impact Factor
  • Antonio Di Sabatino · Gino R Corazza
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2015; DOI:10.1016/j.cgh.2015.07.036 · 7.90 Impact Factor
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    ABSTRACT: INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4+CD25+ subset and increase of the CD3+CD69+ population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-β and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.
    Stem Cell Research & Therapy 07/2015; 6(1). DOI:10.1186/s13287-015-0122-1 · 3.37 Impact Factor
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    ABSTRACT: Many patients with inflammatory bowel disease (IBD) fail to respond to anti-tumor necrosis factor (TNF) agents such as infliximab and adalimumab, and etanercept is not effective in treatment of Crohn's disease. Activated matrix metalloproteinase 3 (MMP3) and MMP12, which are increased in inflamed mucosa of patients with IBD, have a wide range of substrates, including immunoglobulin (Ig)G1. TNF neutralizing agents act in inflamed tissues; we investigated the effects of MMP3, MMP12, and mucosal proteins from IBD patients on these drugs. Biopsies from inflamed colon of 8 patients with Crohn's disease and 8 with ulcerative colitis, and from normal colon of 8 healthy individuals (controls), were analyzed histologically, or homogenized and proteins were extracted. We also analyzed sera from 29 patients with active Crohn's disease and 33 with active ulcerative colitis who were candidates to receive infliximab treatment. Infliximab, adalimumab, and etanercept were incubated with mucosal homogenates from patients with IBD or activated recombinant human MMP3 or MMP12 and analyzed on immunoblots or in luciferase reporter assays designed to measure TNF activity. IgG cleaved by MMP3 or MMP12 and anti-hinge autoantibodies against neo-epitopes on cleaved IgG were measured in sera from IBD patients who subsequently responded (clinical remission and complete mucosal healing) or did not respond to infliximab. MMP3 and MMP12 cleaved infliximab, adalimumab, and etanercept, releasing a 32 kDa Fc monomer. After MMP degradation, infliximab and adalimumab functioned as F(ab')2 fragments, whereas cleaved etanercept lost its ability to neutralize TNF. Proteins from the mucosa of patients with IBD reduced the integrity and function of infliximab, adalimumab, and etanercept. TNF-neutralizing function was restored following incubation of the drugs with MMP inhibitors. Serum levels of endogenous IgG cleaved by MMP3 and MMP12, and anti-hinge autoantibodies against neo-epitopes of cleaved IgG, were higher in patients that did not respond to treatment vs responders. Proteolytic degradation may contribute to non-responsiveness of patients with IBD to anti-TNF agents. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Gastroenterology 07/2015; DOI:10.1053/j.gastro.2015.07.002 · 16.72 Impact Factor
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    ABSTRACT: The belief that hospital stays may constitute per se a risk for patients is not widespread among patients and health care professionals. In the balance between advantages and disadvantages of admission, we rarely take into account the impact of the hospital stay itself on the well-being of the patient. In a society that is getting older the hospital may become a hostile environment for the complex and frail patient. Reducing the risks associated with hospital admission implies a radical cultural change accepted and shared by all health care professionals. The critical reconsideration of admission is a way of reasoning not only on hospitalisation but also on what the correct health outcome paradigms should be. Copyright © 2015. Published by Elsevier B.V.
    European Journal of Internal Medicine 07/2015; 26(7). DOI:10.1016/j.ejim.2015.06.003 · 2.89 Impact Factor
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    ABSTRACT: Whipple's disease (WD) is a rare systemic condition caused, in genetically predisposed subjects, by Tropheryma whipplei, a common bacterium widespread in the environment. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and DQB1*06 and by the demonstration that, in patients with WD, the cytokine genetic profile is skewed toward a Th2 and Treg response. Since IL-16 is involved in hampering the development of a protective macrophagic response against Tropheryma whipplei, we investigated whether the genetic background of IL-16 is different between patients with WD and controls. The -295 T-to-C polymorphism of the promoter region of the IL-16 gene was studied in 90 patients with WD and 152 healthy controls. Levels of serum IL-16 protein were also tested. The frequency of the wild type T allele was significantly higher in patients with WD compared to the controls (155/180 vs. 235/304; p = 0.02 for the Chi(2) test), odds ratio 1.82 [95 % confidence interval (CI) 1.07-3.10]. The TT genotype was found in 65/90 patients with WD and 88/152 controls (p = 0.026). No relationship was found between serum levels of IL-16 and genotypes. Although the functional consequences of this genetic background on levels of IL-16 and on the course of the disease are still unknown, we found, for the first time, that the wild type T allele and the TT genotype of the -295 polymorphism are associated with WD.
    European Journal of Clinical Microbiology 07/2015; 34(9). DOI:10.1007/s10096-015-2433-7 · 2.67 Impact Factor
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    European Journal of Internal Medicine 06/2015; DOI:10.1016/j.ejim.2015.06.007 · 2.89 Impact Factor
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    ABSTRACT: Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ≥2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American journal of cardiology 06/2015; 116(6). DOI:10.1016/j.amjcard.2015.05.060 · 3.28 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy. PATIENTS AND METHODS: Starting from January 10, 2007, through June 30, 2014, clinical evaluation, calculation of the Crohn disease activity index (CDAI), therapeutic management, and documentation of adverse events in 8 of the 10 patients (5 men; median age, 37 years) who had been injected locally with MSCs were prospectively recorded for 72 months. Cumulative probabilities of fistula recurrence and medical or surgical treatment were estimated using a Kaplan-Meier method, whereas differences among the pre- and post-MSC CDAI values were calculated with the Mann-Whitney U test. RESULTS: Following disease remission observed after 12 months from MSC treatment (P<.001), the mean CDAI score increased significantly during the subsequent 2 years (P=.007), and was then followed by a gradual decrease, with the patients achieving remission again (P=.02) at the end of the 5-year follow-up. The probability of fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and 37% during the following 4 years, and the cumulative probabilities of surgery- and medical-free survival were 100% and 88% at 1 year, 75% and 25% at 2, 3, and 4 years, and 63% and 25% at 5 and 6 years, respectively. No adverse events were recorded. CONCLUSION: Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.
    Mayo Clinic Proceedings 06/2015; 90(6). DOI:10.1016/j.mayocp.2015.03.023. · 6.26 Impact Factor
  • S Basili · M Proietti · F Perticone · G R Corazza · F Violi
    Thrombosis and Haemostasis 05/2015; 114(3). DOI:10.1160/TH15-02-0101 · 4.98 Impact Factor
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    ABSTRACT: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). Observational prospective multicentre cohort study. Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. 897 AF patients on treatment with vitamin K antagonists. The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR<60 mL/min/1.73 m(2). Annual decline of eGFR was -2.0 (IQR -7.4/-0.4) mL/min/1.73 m(2)/year, and 32.4% patients had a rapid decline in eGFR. Multivariable logistic regression analysis showed that ABI ≤0.90 (OR 1.516 (95% CI 1.075 to 2.139), p=0.018) and arterial hypertension (OR 1.830 95% CI 1.113 to 3.009, p=0.017) predicted a rapid eGFR decline, with an inverse association for angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (OR 0.662 95% CI 0.464 to 0.944, p=0.023). Among the 639 patients with AF with eGFR >60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration. NCT01161251. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    BMJ Open 05/2015; 5(5):e008026-e008026. DOI:10.1136/bmjopen-2015-008026 · 2.27 Impact Factor
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    ABSTRACT: The relationship between gluten ingestion and gastrointestinal tract function is a matter of debate. We analysed the effect of gluten on gastric and gallbladder emptying and intestinal fermentation in healthy volunteers. Ultrasound measurement of gastric and gallbladder emptying after both gluten-containing and gluten-free meals was performed in 18 volunteers (8 women, age 25.0±2.5 years; BMI 22±1.9). Breath hydrogen excretion after a gluten-containing meal, a gluten-free meal and a gluten-free meal with added gluten powder was measured in 16 volunteers (10 women, age 25.2±2.7 years; BMI 22±1.8). The severity of symptoms was monitored. Gluten presence in the meals was not recognised. Gastric emptying time was 81.6±13.8min after gluten-containing and 73.9±21.6min after gluten-free meals (p=0.11). Percentage ejection fraction after gluten-containing meals was 60±9% and 60.6±6% after gluten-free meals (p=0.68). Peak and cumulative hydrogen excretion were significantly higher after gluten-containing than after gluten-free meals (peak: 12.5±7.3 vs 6.5±5.1 parts-per-million, p<0.01; and cumulative: 2319±1720 vs 989±680 parts-per-million/minute, respectively; p<0.01). Adding gluten powder to the gluten-free meal did not modify fermentation. Symptoms were mild and not different after the meals. In healthy volunteers, gluten may induce gastrointestinal alterations. Further studies are needed to clarify which patients could benefit from dietary modification. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
    Digestive and Liver Disease 05/2015; 47(9). DOI:10.1016/j.dld.2015.05.013 · 2.96 Impact Factor
  • Michela Masotti · Gaetano Bergamaschi · Pietro Formagnana · Gino Roberto Corazza
    Internal and Emergency Medicine 05/2015; 10(5). DOI:10.1007/s11739-015-1240-6 · 2.62 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-328. DOI:10.1016/S0016-5085(15)31087-8 · 16.72 Impact Factor
  • F Biagi · D Balduzzi · P Delvino · A Schiepatti · C Klersy · G R Corazza
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    ABSTRACT: Whipple's disease (WD) is a rare systemic infection due, in genetically susceptible individuals, to Tropheryma whipplei, a heterogeneous Gram-positive actinobacteria. Although it has already been recognised that WD affects mainly middle-aged Caucasian men, the prevalence of WD is virtually unknown. The annual incidence of WD in the general population is said to be less than 1 per 1,000,000, but scientific evidence for these figures is still lacking. On the basis of the number of patients recorded with a diagnosis of Whipple's disease in the regional registers for rare diseases of Lombardia, Liguria and Piemonte-Valle d'Aosta regions, we studied the prevalence of WD in the north-western part of Italy. Forty-six patients with Whipple's disease were recorded in these regions (13 females; mean age at diagnosis 52.1 ± 11.1 years). Since 16,130,725 inhabitants live in these four regions, prevalence of WD in the general population is 3/10(6) and almost 30 % of the patients are females. WD is certainly a rare disease but it also affects women in a considerable proportion of cases.
    European Journal of Clinical Microbiology 03/2015; 34(7). DOI:10.1007/s10096-015-2357-2 · 2.67 Impact Factor
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    ABSTRACT: Objectives: The role of colonic methane production in functional bowel disorders is still uncertain. In small samples of irritable bowel syndrome (IBS) patients, it was shown that methane breath excretion correlates with clinical presentation and delayed gastrointestinal transit time. The aim of this study was to evaluate the relationship between intestinal production and breath excretion of CH4 and to correlate CH4 production with the presence and the severity of symptoms, in a large cohort of IBS patients and in a group of healthy volunteers. Methods: A group of 103 IBS patients and a group of 28 healthy volunteers were enrolled. The presence and severity of symptoms and gastrointestinal transit were evaluated in all subjects, who underwent breath H2/CH4 measurement for 7 h after lactulose to identify breath excretors of these gases; H2 and CH4 were also measured in rectal samples to identify colonic producers. Cumulative H2 and CH4 excretion and production were evaluated by the area under the time-concentration curve calculation (AUC). Results: In IBS patients, CH4 was detected in rectal samples in 48 patients (47%), but only 27 of them (26% of the 103 enrolled patients) excreted this gas with breath. In CH4 producers, the prevalence and severity of symptoms and gastrointestinal transit time were not significantly different with respect to non-producers. IBS subtypes were homogeneously represented in CH4 producers and in non-producers. Healthy volunteers, compared with IBS patients, showed a significantly lower prevalence of CH4 excretion, whereas no difference was found in the prevalence of colonic CH4 production; moreover, in healthy volunteers compared with IBS, CH4 breath excretion and CH4 production were not different in quantitative terms. Conclusion: Our data show that colonic CH4 production is not associated with clinical presentation in IBS patients and does not correlate with symptom severity or with gastrointestinal transit time. Clinical inferences based on breath CH4 excretion should undergo an in-depth revision, as this method is not a good marker of CH4 colonic production.
    The American Journal of Gastroenterology 03/2015; 110(6). DOI:10.1038/ajg.2015.47 · 10.76 Impact Factor
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    ABSTRACT: Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).
    New England Journal of Medicine 03/2015; 372(12):1104-13. DOI:10.1056/NEJMoa1407250 · 55.87 Impact Factor
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    ABSTRACT: BACKGROUND: RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity. METHODS: We enrolled 60 CD, 67 UC patients, and 66 controls (all adults). Disease activity was scored through the clinical, endoscopic, and histologic indexes of severity, whilst disease location and behaviour were assessed according to the Montreal classification. In all cases, the levels of serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured. RESULTS: sRAGE levels were significantly lower in UC, both active and inactive, than in controls and CD (817.35, range 437.3-1449; 1211, range 843.7-1618; 1207.5, range 743.15-1875.75; P < 0.05 for both), and inversely correlated with clinical and endoscopic indexes of activity in both IBD groups (P < 0.05 for all) and with the histologic score in the CD group. Moreover, those CD patients with a penetrating behaviour showed a significant reduction in both sRAGE (P = 0.006) and S100A12 (P = 0.034) as compared to those with an inflammatory/stricturing pattern. Although S100A12 levels were not found up-regulated, a negative correlation appeared evident with the clinical (r = -0.38) and endoscopic (r = -0.32) indexes of activity in UC and CD, respectively. CONCLUSION: These data suggest a different role for RAGE in CD and UC, and a potential use of sRAGE as a new biomarker.
    Digestive Diseases and Sciences 03/2015; · 2.61 Impact Factor

Publication Stats

9k Citations
3,546.62 Total Impact Points


  • 1999–2015
    • University of Pavia
      • • Department of Public Health, Experimental and Forensic Medicine
      • • Department of Molecular Medicine
      Ticinum, Lombardy, Italy
  • 2001–2014
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 2013
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 1981–2013
    • University of Bologna
      • • "Guglielmo Marconi" Department of Electrical, Electronic and Information Engineering DEI
      • • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy
  • 2009
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • Ospedale Pediatrico Bambino Gesù
      Roma, Latium, Italy
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 2008
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 2007
    • University of Florence
      Florens, Tuscany, Italy
  • 1991–2007
    • Università degli Studi dell'Aquila
      • • Department of Experimental Medicine
      • • SS in Clinical Pathology
      • • SS in Internal Medicine
      • • Department of Internal Medicine and Public Health
      Aquila, Abruzzo, Italy
  • 2006
    • Università Cattolica del Sacro Cuore
      Milano, Lombardy, Italy
  • 2002
    • University of Maryland, Baltimore
      • Center for Celiac Research
      Baltimore, Maryland, United States
  • 1998
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1997
    • Catholic University of the Sacred Heart
      • Institute of Internal and Geriatric Medicine
      Milano, Lombardy, Italy
  • 1995–1997
    • University of Milan
      Milano, Lombardy, Italy
  • 1993
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
    • University of Adelaide
      Tarndarnya, South Australia, Australia