Francesco Pallone

University of Rome Tor Vergata, Roma, Latium, Italy

Are you Francesco Pallone?

Claim your profile

Publications (503)2521.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: : The etiologies of Crohn's disease and ulcerative colitis, the 2 major forms of inflammatory bowel disease in humans, remain unknown, but experimental studies suggest that inflammatory bowel disease results from interaction between environmental and genetic factors, which promotes an exaggerated and inappropriately controlled inflammatory response that is directed against normal components of the gut flora. There is also evidence that tissue damage is due to a dynamic interplay between immune and nonimmune cells, and recruitment of lymphocytes from the blood stream to the gut wall is crucial for amplifying and sustaining the ongoing mucosal inflammation. These advances have led to the development of several compounds blocking gut homing of effector lymphocytes, which have recently been used or are now ready to move into clinical practice. This article summarizes the recent data on the use of integrin-targeting and adhesion molecule-targeting therapeutics to attenuate the detrimental inflammatory response in inflammatory bowel disease.
    Inflammatory Bowel Diseases 10/2014; 20(10):1885-1889. · 5.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC) is the fourth most common cancer in the world and the second cause of cancer-related death. Gastric carcinogenesis is a multifactorial process, in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC cells. One such a pathway is regulated by proteinase activated-receptors (PARs), seven transmembrane-spanning domain G protein-coupled receptors, which comprise four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4) activated by various proteases. Both PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways, which sustain gastric carcinogenesis. There is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of patients. Consistently, data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC patients. In contrast, PAR-4 levels are down-regulated in GC and correlate inversely with the aggressiveness of GC, thus suggesting a negative role of this receptor in the control of GC. In this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior.
    World journal of gastroenterology : WJG. 09/2014; 20(34):11977-11984.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancers (CRCs) often show a dense infiltrate of cytokine-producing immune/inflammatory cells. The exact contribution of each immune cell subset and cytokine in the activation of the intracellular pathways sustaining CRC cell growth is not understood. Herein, we isolate tumor-infiltrating leukocytes (TILs) and lamina propria mononuclear cells (LPMCs) from the tumor area and the macroscopically unaffected, adjacent, colonic mucosa of patients who underwent resection for sporadic CRC and show that the culture supernatants of TILs, but not of LPMCs, potently enhance the growth of human CRC cell lines through the activation of the oncogenic transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kB). Characterization of immune cell complexity of TILs and LPMCs reveals no differences in the percentages of T cells, natural killer T cells, natural killer (NK) cells, macrophages and B cells. However, T cells from TILs show a functional switch compared with those from LPMCs to produce large amounts of T helper type 17 (Th17)-related cytokines (that is, interleukin-17A (IL-17A), IL-17F, IL-21 and IL-22), tumor necrosis factor-α (TNF-α) and IL-6. Individual neutralization of IL-17A, IL-17F, IL-21, IL-22, TNF-α or IL-6 does not change TIL-derived supernatant-driven STAT3 and NF-kB activation, as well as their proproliferative effect in CRC cells. In contrast, simultaneous neutralization of both IL-17A and TNF-α, which abrogates NF-kB signaling, and IL-22 and IL-6, which abrogates STAT3 signaling, reduces the mitogenic effect of supernatants in CRC cells. IL-17A, IL-21, IL-22, TNF-α and IL-6 are also produced in excess in the early colonic lesions in a mouse model of sporadic CRC, associated with enhanced STAT3/NF-kB activation. Mice therapeutically given BP-1-102, an orally bioavailable compound targeting STAT3/NF-kB activation and cross-talk, exhibit reduced colon tumorigenesis and diminished expression of STAT3/NF-kB-activating cytokines in the neoplastic areas. These data suggest that strategies aimed at the cotargeting of STAT3/NF-kB activation and interaction between them might represent an attractive and novel approach to combat CRC.Oncogene advance online publication, 1 September 2014; doi:10.1038/onc.2014.286.
    Oncogene 09/2014; · 8.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: IL-21, a cytokine produced by activated CD4+ cells, activated natural killer T cells and T helper cells in the germinal centers, is involved in the control of the function of both immune and parenchymal cells.Areas covered: IL-21 is overproduced in many chronic inflammatory disorders, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, type I diabetes and systemic lupus erythematosus, and studies in experimental models indicate that IL-21 plays an important role in sustaining tissue-damaging immune responses in such pathologies. However, genetic deficiency of IL-21 associates with inflammatory bowel diseases and blockade of IL-21 in the early phases exacerbates the disease progression in some models of rheumatoid arthritis and systemic lupus erythematosus, thus suggesting a dual role of IL-21 in the control of immune-mediated diseases. IL-21 can exert additional protective functions for the host as it promotes cytotoxic responses against tumors and viruses.Expert opinion: We here review the available data on the role of IL-21 in chronic inflammatory diseases and discuss the therapeutic benefit of IL-21 inhibitors in such diseases as well as the potential risks of such treatments.
    Expert Opinion on Therapeutic Targets. 08/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time-consuming procedures to make a final diagnosis. Regenerating islet-derived 3-alpha (Reg3α) is detectable in the circulation of patients with intestinal graft-versus host disease and patients with inflammatory bowel disease (IBD).AimTo determine whether serum Reg3α testing is useful for discriminating mucosal enteropathies from functional intestinal disorders.Methods We prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and after 6–12 months of a gluten-free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut-off value. Reg3α levels were measured by a commercial ELISA kit.ResultsLevels of Reg3α exceeded the cut-off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC patients and one patient with IBS(4%). Reg3α levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3α levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX.Conclusion Reg3α is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies.
    Alimentary Pharmacology & Therapeutics 08/2014; · 4.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colonic metaplasia has been described in pouchitis. In a prospective study, we investigated whether colonic phenotype may develop in Crohn's disease (CD) ileum. The expression of sulfomucins (colonic mucin), sialomucins, and CD10 (small intestine mucin and phenotype) was evaluated before and after ileocolonic resection for CD.
    Inflammatory Bowel Diseases 07/2014; · 5.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In inflammatory bowel disease (IBD), tissue damage is driven by an excessive immune response, poorly controlled by counter-regulatory mechanisms. SIRT1, a class III NAD+-dependent deacetylase, regulates negatively the expression of various proteins involved in the control of immune-inflammatory pathways, such as Stat3, Smad7, and NF-κB. Here we examined the expression, regulation, and function of SIRT1 in IBD. SIRT1 RNA and protein expression was less pronounced in whole biopsies and lamina propria mononuclear cells (LPMCs) of IBD patients in comparison with normal controls. SIRT1 expression was downregulated in control LPMC by tumor necrosis factor (TNF)-α and interleukin (IL)-21, and upregulated in IBD LPMC by neutralizing TNF-α and IL-21antibodies. Consistently, SIRT1 expression was increased in mucosal samples taken from IBD patients successfully treated with Infliximab. Treatment of IBD LPMC with Cay10591, a specific SIRT1 activator, reduced NF-κB activation and inhibited inflammatory cytokine synthesis, whereas Ex527, an inhibitor of SIRT1, increased interferon (IFN)-γ in control LPMC. SIRT1 was also reduced in mice with colitis induced by 2,4,6-trinitrobenzenesulphonic acid or oxazolone. Cay10591 prevented and cured experimental colitis whereas Ex527 exacerbated disease by modulating T cell-derived cytokine response. Data indicate that SIRT1 is downregulated in IBD patients and colitic mice and suggest that SIRT1 activation can help attenuate inflammatory signals in the gut.Mucosal Immunology advance online publication, 21 May 2014; doi:10.1038/mi.2014.35.
    Mucosal Immunology 05/2014; · 7.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In both Crohn's disease (CD) and ulcerative colitis (UC), the gut is massively infiltrated with B cells and plasma cells, but the role of these cell types in the pathogenesis of gut tissue damage remains largely unknown. Human B cells express granzyme B (GrB) when cultured with IL-21, a cytokine overproduced in CD and UC mucosa. We therefore examined whether mucosal B cells express GrB and have cytotoxic activity in inflammatory bowel disease (IBD). GrB-expressing CD19(+) and IgA(+) cells were seen in the normal intestinal mucosa, but they were significantly more frequent in both CD and UC. In contrast, only a minority of CD19(+) and IgA(+) cells expressed perforin with no difference between IBD and controls. GrB-producing CD19(+) cells expressed CD27 and were CD38(high) and CD20 negative. CD19(+) B cells from IBD patients induced HCT-116 cell death. IL-21 enhanced GrB expression in control CD19(+) B cells and increased their cytotoxic activity. These data indicate that IBD-related inflammation is marked by mucosal accumulation of cytotoxic, GrB-expressing CD19(+) and IgA(+) cells, suggesting a role for these cells in IBD-associated epithelial damage.
    Digestive and Liver Disease 05/2014; · 3.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic antibodies against tumor necrosis factor 〈 (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but the little is known about the effects of anti-TNF agents on structural damage in the intestine. Small intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD, SLIC) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index (CDAI) scores<150. Results. We observed significant improvements in SLIC scores and sub-scores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and sub-scores and index classes were significantly improved in patients with vs without clinical responses. Controls had no improvements in terms of CDAI or SLIC scores, or index classes. Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2014; · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transforming Growth Factor (TGF-)-Beta is deeply involved in colorectal cancer development and the disruption of the TGF-beta signaling in dysplastic cells is required for tumor to grow. Nevertheless, tumor cells express TGF-beta to escape the immune-surveillance mediated by T cells. T cell expression of Smad7, an intracellular inhibitor of the TGF-beta signaling, protects against colitis-associated colorectal cancer. However whether Smad7 in T cells might influence colorectal cancer growth independently of chronic inflammation and which T cell subset is involved in this process, is unknown. To address this issue, T cell-specific Smad7 transgenic mice and wild type littermates were subcutaneously transplanted with syngenic MC38 colon carcinoma cells. Smad7Tg mice were resistant to tumor development compared to wild type mice and protection was dependent on CD4+ T cells. Smad7 expression in T cells increased the number of tumor-infiltrating T-bet/ROR-gamma-t double positive CD4 T cells characterized by the expression of TNF-alpha and IFN-gamma but lower IL-17A. The low expression of IL17A caused by the Smad7 expression in tumor infiltrating CD4+ T cells enabled the TNF-alpha-mediated killing of cancer cells both in vitro and in vivo thus indicating that the Smad7-mediated plastic effect on T cell phenotype induces protection against colorectal cancer.
    Carcinogenesis 01/2014; · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ghrelin, the ligand of growth hormone secretagogue receptor 1a, takes part in several functions of the digestive system, including regulation of appetite, energy homeostasis, gastric acid secretion and motility. Ghrelin has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric damage. Interestingly, ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori (H. pylori) infection, a worldwide condition inducing a T helper (Th)1/Th17 cell response-driven gastritis, which may evolve towards gastric atrophy and cancer. In this article, we review the available data on the expression of ghrelin in H. pylori infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.
    World Journal of Gastroenterology 01/2014; 20(3):639-646. · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since celiac disease-associated mucosal lesions are patchy, the diagnosis of the disease requires histological evaluation of multiple duodenal biopsies. To examine whether adequate biopsy sampling in either the bulb or distal duodenum is sufficient to diagnose celiac disease. Twenty-five patients with positive celiac disease-specific serology and 17 patients with negative serology, who were on a gluten-containing diet, and 13 celiac disease patients on a gluten-free diet were consecutively and prospectively enrolled. Mucosal damage, anti-transglutaminase-2 IgA deposits, interferon-γ, interleukin-17A and interleukin-15 transcripts were evaluated in bulb and distal duodenal biopsies. All patients with positive celiac disease-specific serology exhibited villous atrophy in both duodenal sites. In this group, mucosal anti-transglutaminase-2 IgA deposits were found in 24/25 (96%) bulb samples and 22/25 (88%) distal duodenal samples. No villous atrophy was documented in patients with negative serology. Interferon-γ and interleukin-17A were over-expressed in both duodenal sites of patients with villous atrophy, unlike patients with normal duodenal morphology (p<0.001). Among treated celiac disease patients, 2 (15.4%) had villous atrophy exclusively in the bulb and 6 (46.2%) had minimal histological abnormalities at both sites. Sampling in the bulb and distal duodenum could be sufficient to diagnose/exclude celiac disease.
    Digestive and Liver Disease 01/2014; · 3.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Innate lymphoid cells (ILCs) are a group of hematopoietic cells devoid of antigen receptors that have important functions in lymphoid organogenesis, in the defense against extracellular pathogens, and in the maintenance of the epithelial barrier. Three distinct groups of ILCs have been identified on the basis of phenotypic and functional criteria and termed ILCs1, ILCs2, and ILCs3. Specifically, ILCs1 express the transcription factor T-bet and secrete T helper type-1- (Th1-) related cytokines, ILCs2 are dependent on the transcription factor RORα and express Gata-3 and the chemokine receptor homologous molecule (CRTH2) and produce Th2-related cytokines, and ILCs3 express the transcription factor RORγt and synthesize interleukin- (IL-) 17, IL-22, and, under specific stimuli, interferon-γ. ILCs represent a relatively small population in the gut, but accumulating evidence suggests that these cells could play a decisive role in orchestrating both protective and detrimental immune responses. In this review, we will summarize the present knowledge on the distribution of ILCs in the intestinal mucosa, with particular focus on their role in the control of both infections and effector cytokine response in immune-mediated pathologies.
    Mediators of Inflammation 01/2014; 2014:235460. · 3.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Initially identified as an inhibitor of transforming growth factor (TGF)-β mainly owing to its ability to bind TGF-β receptor type I and abrogate TGF-β-driven signaling, Smad7 can interact with additional intracellular proteins and regulate TGF-β-independent pathways, thus having a key role in the control of neoplastic processes in various organs. Genome-wide association studies have shown that common alleles of Smad7 influence the risk of colorectal cancer (CRC), even though the contribution of Smad7 in colon carcinogenesis is not fully understood. In this study, we assessed the expression and role of Smad7 in human and mouse models of sporadic CRC. We document a significant increase of Smad7 in human CRC relative to the surrounding nontumor tissues and show that silencing of Smad7 inhibits the growth of CRC cell lines both in vitro and in vivo after transplantation into immunodeficient mice. Knockdown of Smad7 results in enhanced phosphorylation of the cyclin-dependent kinase (CDK)2, accumulation of CRC cells in S phase and enhanced cell death. Smad7-deficient CRC cells have lower levels of CDC25A, a phosphatase that dephosphorylates CDK2, and hyperphosphorylated eukaryotic initiation factor 2 (eIF2)α, a negative regulator of CDC25 protein translation. Consistently, knockdown of Smad7 associates with inactivation of eIF2α, lower CDC25A expression and diminished fraction of proliferating cells in human CRC explants, and reduces the number of intestinal tumors in Apc(min/+) mice. Altogether, these data support a role for Smad7 in sustaining colon tumorigenesis.
    Cell Death & Disease 01/2014; 5:e1073. · 6.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & Aims Therapeutic antibodies against tumor necrosis factor 〈 (anti-TNF) are effective in patients with Crohn’s disease (CD). Mucosal healing is a surrogate marker of efficacy, but the little is known about the effects of anti-TNF agents on structural damage in the intestine. Small intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD, SLIC) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. Methods We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index (CDAI) scores<150. Results. We observed significant improvements in SLIC scores and sub-scores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and sub-scores and index classes were significantly improved in patients with vs without clinical responses. Controls had no improvements in terms of CDAI or SLIC scores, or index classes. Conclusion Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD.
    Clinical Gastroenterology and Hepatology. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Discrepancies between severity of lesions and symptoms may be observed in Crohn's disease. We prospectively assessed whether Crohn's disease may be diagnosed among asymptomatic relatives of patients, using Small Bowel Contrast Ultrasonography. Diagnosis of asymptomatic Crohn's disease relatives was defined ultrasonographically as: bowel wall thickness >3mm, bowel dilation/stricture, lumen diameter >2.5cm. Diagnosis was confirmed by ileocolonoscopy. Subjects were also screened for the Leu3020insC mutation. Consent was given by 35 asymptomatic first-degree relatives of 18 Crohn's disease patients. Ultrasonography indicated increased bowel wall thickness (5mm) compatible with ileal Crohn's disease in 1 relative (2.8%), a 42 year-old male. Ileocolonoscopy, histology, and radiology confirmed the diagnosis of stricturing ileal Crohn's disease. Gallbladder stones were detected in 7/35 (20%) relatives and Leu3020insC mutation in 3/35 (8.5%). Small Bowel Contrast Ultrasonography may be a useful tool to diagnose asymptomatic small bowel Crohn's disease among first-degree relatives of patients.
    Digestive and Liver Disease 12/2013; · 3.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immune/inflammatory cells infiltrate almost all human solid tumors and affect all stages of carcinogenesis as they produce different cytokine subsets. The overproduction of TH17 cytokines marks the early stages of colorectal carcinoma (CRC) and negatively influences the prognosis of CRC patients. Studies with murine models of CRC have delineated the mechanisms by which TH17 cytokines, notably, interleukin (IL)-17A, IL-17F, IL-21, and IL-22, regulate oncogenesis and tumor progression, paving the way to the development of novel anticancer drugs. In this review article, we discuss experimental data supporting the role of TH17 cytokines in the modulation of colorectal tumorigenesis.
    Oncoimmunology. 12/2013; 2(12):e26617.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis characterized by painful cutaneous ulcerations and often associated with systemic inflammatory and neoplastic diseases. Here we report the first case of pyoderma gangrenosum in a patient with refractory celiac disease. A 52-year-old woman with a previously diagnosed refractory celiac disease resistant to steroids and immunosuppressive drugs presented to our hospital for a rapidly growing, painful inflammatory skin lesion of the left leg. Physical examination revealed a painful lesion with focal ulceration, necrosis and pus discharge with active inflammatory borders at the external part of the left leg. Histological evaluation of a skin biopsy and analysis of inflammatory cytokines and matrix-degrading proteases in lesional skin samples confirmed the clinical suspicion of pyoderma gangrenosum. Treatment with oral prednisone was rapidly followed by a complete healing of the skin lesion but no improvement of symptoms/signs of malabsorption. Treatment of the patient with systemic steroids healed the skin lesion without improving the underlying refractory celiac disease. This observation raises the possibility that refractory celiac disease and pyoderma gangrenosum may be immunologically different.
    BMC Gastroenterology 11/2013; 13(1):162. · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reduced levels of iron, folate, vitamin B12, vitamin D, zinc, and magnesium are common in untreated celiac disease (CD) patients probably due to loss of brush border proteins and enzymes needed for the absorption of these nutrients. In the majority of patients, removal of gluten from the diet leads to histological recovery and normalization of iron, vitamin, and mineral levels. Iron deficiency anemia is the most common extra-intestinal sign of CD and usually resolves with adherence to a gluten-free diet. However, deficiencies of both folate and vitamin B12 may persist in some patients on a gluten-free diet, thus requiring vitamin supplementation to improve subjective health status. Similarly, exclusion of gluten from the diet does not always normalize bone mineral density; in these cases, supplementation of vitamin D and calcium is recommended. Resolution of mucosal inflammation may not be sufficient to abrogate magnesium deficiency. Since gluten-free cereal products have a lower magnesium content as compared with gluten-containing counterparts, a magnesium-enriched diet should be encouraged in CD patients. In this article we discuss the frequency and clinical relevance of nutrient deficiency in CD and whether and when nutrient supplementation is needed.
    Annals of Medicine 11/2013; · 4.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Refractory celiac disease (RCD) is characterized by severe symptoms/signs of malabsorption and mucosal damage unresponsive to a gluten-free diet. The pathogenesis of RCD is not fully understood. Here we characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies were taken from patients with RCD, patients with active CD, and normal controls, and analyzed for inflammatory cytokines by real-time PCR and ELISA. IFN-γ and IL-21 transcripts were increased in active CD patients but not in RCD patients as compared to normal controls, while IL-17A RNA was up-regulated in both active CD and RCD. No significant increase in IL-15 transcripts was seen in both active CD and RCD, while IL-15 protein was increased in active CD. IL-6 and TNF-α were up-regulated only in RCD. As a proof, we present the case of a woman affected by RCD who responded to anti-TNF-α treatment with improvement of malabsorptive symptoms/signs but no healing of mucosal lesions. Data indicate that the profile of mucosal effector cytokines differs between RCD and active CD and suggest that TNF-α, IL-6 and IL-17A, but not Th1-type cytokines, could drive the detrimental response in this condition.
    Clinical Science 10/2013; · 4.86 Impact Factor

Publication Stats

8k Citations
2,521.12 Total Impact Points

Institutions

  • 1999–2014
    • University of Rome Tor Vergata
      • • Dipartimento di Medicina dei Sistemi
      • • Centro di Eccellenza per lo Studio del Rischio Genomico in Patologie Complesse Multifattoriali
      Roma, Latium, Italy
  • 2011
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      Milano, Lombardy, Italy
  • 2007
    • Policlinico Tor Vergata
      • Medicina Interna
      Roma, Latium, Italy
  • 1996–2007
    • Istituto Superiore di Sanità
      • Laboratory of Virology
      Roma, Latium, Italy
  • 1991–2007
    • Universita' degli Studi "Magna Græcia" di Catanzaro
      • Department of Health Sciences
      Catanzaro, Calabria, Italy
  • 2003
    • National Research Council
      • Institute of Food Sciences ISA
      Roma, Latium, Italy
    • University of Naples Federico II
      • Department of Translational Medical Sciences
      Napoli, Campania, Italy
  • 2001–2003
    • LIUCBM Libera Università Campus Bio-Medico di Roma
      Roma, Latium, Italy
  • 2002
    • Università degli Studi Europea di Roma
      Roma, Latium, Italy
  • 1984–2000
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
  • 1995–1997
    • Mediterranean University of Reggio Calabria
      Reggio di Calabria, Calabria, Italy
  • 1990
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1985–1988
    • Umberto I Policlinico di Roma
      Roma, Latium, Italy
  • 1981–1986
    • The American University of Rome
      Roma, Latium, Italy