@article {10416, title = {Anti-transglutaminase 6 Antibody Development in Children With Celiac Disease Correlates With Duration of Gluten Exposure.}, journal = {J Pediatr Gastroenterol Nutr}, volume = {66}, year = {2018}, month = {2018 Jan}, pages = {64-68}, abstract = {

OBJECTIVES: Antibodies against transglutaminase 6 (anti-TG6) have been implicated in neurological manifestations in adult patients with genetic gluten intolerance, and it is unclear whether autoimmunity to TG6 develops following prolonged gluten exposure. We measured the anti-TG6 in children with celiac disease (CD) at the diagnosis time to establish a correlation between these autoantibodies and the duration of gluten exposure. We investigated a correlation between anti-TG6 and the presence of neurological disorders.

METHODS: Anti-TG6 (IgA/IgG) were measured by ELISA in sera of children with biopsy-proven CD and of children experiencing gastrointestinal disorders. CD patients positive for anti-TG6 were retested after 2 years of gluten-free diet (GFD).

RESULTS: We analyzed the sera of 274 CD children and of 121 controls. Anti-TG6 were detected in 68/274 (25\%) CD patients and in 19/121 (16\%) controls, with significant difference between the 2 groups (P = 0.04). None of the CD patients and of the controls testing positive for anti-TG6 were experiencing neurological disorders. Eleven of 18 (61\%) CD patients with other autoimmune diseases were positive for anti-TG6. In CD patients, a significant correlation between the gluten exposure before the CD diagnosis and anti-TG6 concentration was found (P = 0.006 for IgA; P < 0.0001 for IgG). After GFD anti-TG6 concentrations were significantly reduced (P < 0.001). No significant correlation was observed between anti-TG6 and anti-TG2 serum concentrations.

CONCLUSIONS: Anti-TG6 are more prevalent in children with untreated CD in the absence of overt neurological disorders. The synthesis of the anti-TG6 is related to a longer exposure to gluten before the CD diagnosis, and the autoimmunity against TG6 is gluten dependent and disappeared during GFD.

}, issn = {1536-4801}, doi = {10.1097/MPG.0000000000001642}, author = {De Leo, Luigina and Aeschlimann, Daniel and Hadjivassiliou, Marios and Aeschlimann, Pascale and Salce, Nicola and Vatta, Serena and Ziberna, Fabiana and Cozzi, Giorgio and Martelossi, Stefano and Ventura, Alessandro and Not, Tarcisio} } @article {7765, title = {An adolescent with an altered state of mind.}, journal = {BMJ}, volume = {350}, year = {2015}, month = {2015}, pages = {h299}, keywords = {Adolescent, Cannabinoids, Designer Drugs, Hallucinations, Humans, Male, Substance-Related Disorders}, issn = {1756-1833}, doi = {10.1136/bmj.h299}, author = {Naviglio, Samuele and Papanti, Duccio and Moressa, Valentina and Ventura, Alessandro} } @article {3556, title = {Association between orofacial granulomatosis and Crohn{\textquoteright}s disease in children: systematic review.}, journal = {World J Gastroenterol}, volume = {20}, year = {2014}, month = {2014 Jun 21}, pages = {7497-504}, abstract = {

AIM: To review pediatric cases of orofacial granulomatosis (OFG), report disease characteristics, and explore the association between OFG and Crohn{\textquoteright}s disease.

METHODS: We conducted a systematic review according to the PRISMA guidelines. We searched Medline, LILACS, Virtual Health Library, and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range (< 18 years), with no language limitations. All relevant articles were accessed in full text. The manual search included references of retrieved articles. We extracted data on patients{\textquoteright} characteristics, disease characteristics, association with other diseases, and treatment. We analyzed the data and reported the results in tables and text.

RESULTS: We retrieved 173 reports of OFG in children. Mean age at onset was 11.1 {\textpm} 3.8 years (range: 2.0-18 years). Prevalence in males was significant higher than in females (P < 0.001), with a male:female ratio of 2:1. Gastrointestinal signs or symptoms were present in 26.0\% of children at the time of OFG diagnosis. Overall, 70/173 (40.4\%) children received a concomitant diagnosis of Crohn{\textquoteright}s disease. In about half (51.4\%) of the cases the onset of OFG anticipated the diagnosis of Crohn{\textquoteright}s disease, with a mean time between the two diagnoses of 13.1 {\textpm} 11.6 mo (range: 3-36 mo). Overall, 21/173 (12.1\%) of the children with OFG had perianal disease, while 11/173 (6.4\%) had a family history of Crohn{\textquoteright}s disease. Both perianal disease and a family history of Crohn{\textquoteright}s disease were significantly associated with a higher risk of Crohn{\textquoteright}s disease diagnosis in children with OFG [relative risk (RR) = 3.10, 95\% confidence interval (CI): 2.46-3.90; RR = 2.74, 95\%CI: 2.24-3.36, P < 0.0001 for both). Treatment of OFG included steroids (70.8\% of children) and other immunosuppressive drugs (42.7\%), such as azathioprine, thalidomide and infliximab.

CONCLUSION: High prevalence of Crohn{\textquoteright}s disease in children with OFG suggests that OFG may be a subtype of Crohn{\textquoteright}s disease.

}, keywords = {Adolescent, Age of Onset, Child, Child, Preschool, Crohn Disease, Female, Granulomatosis, Orofacial, Humans, Immunosuppressive Agents, Male, Prevalence, Risk Factors, Steroids, Treatment Outcome}, issn = {2219-2840}, doi = {10.3748/wjg.v20.i23.7497}, author = {Lazzerini, Marzia and Bramuzzo, Matteo and Ventura, Alessandro} } @article {1796, title = {Amenorrhea in women treated with thalidomide: report of two cases and literature review.}, journal = {Inflamm Bowel Dis}, volume = {19}, year = {2013}, month = {2013 Jan}, pages = {E10-1}, keywords = {Adolescent, Amenorrhea, Colitis, Ulcerative, Crohn Disease, Female, Humans, Review Literature as Topic, Thalidomide}, issn = {1536-4844}, doi = {10.1002/ibd.22845}, author = {Lazzerini, Marzia and Bramuzzo, Matteo and Martelossi, Stefano and Magazz{\`u}, Giuseppe and Pellegrino, Salvatore and Ventura, Alessandro} } @article {1977, title = {Acute and recurrent pancreatitis in children: exploring etiological factors.}, journal = {Scand J Gastroenterol}, volume = {47}, year = {2012}, month = {2012 Dec}, pages = {1501-4}, abstract = {

OBJECTIVE: Etiologies of acute pancreatitis (AP) in children are more variable than in adults, including drugs, traumas, infections and multisystem disorders as well as biliary anomalies. While causes of pancreatitis have been extensively analyzed, different series reported different causes. The aims of this study were: 1) to assess the etiological factors of acute and recurrent pancreatitis in a pediatric population from a tertiary care hospital; 2) to assess the usefulness of imaging studies in diagnosing etiologies of pancreatitis.

MATERIAL AND METHODS: Thirty-four children (median age 11 years, 23 males) with AP and 11 with recurrent pancreatitis were retrospectively studied to assess etiology of pancreatitis in children.

RESULTS: The most common etiologies of AP were medications (11/34) and biliary tract diseases (9/34), whereas systemic diseases accounted for a small percentage of case. Among patients with recurrent episodes, biliary anomalies were the most common cause (6/11), whereas only 2 out of 11 patients with recurrent pancreatitis presented a hereditary cause.

CONCLUSIONS: This study highlights that etiologies of AP in children are variable. Epidemiology of AP could be influenced by single center{\textquoteright}s characteristics. Anatomic anomalies should be ruled out and genetic causes should be considered in recurrent cases.

}, keywords = {Adolescent, Azathioprine, Biliary Tract, Biliary Tract Diseases, Carrier Proteins, Child, Child, Preschool, Cholangiography, Cholangiopancreatography, Endoscopic Retrograde, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Immunosuppressive Agents, Magnetic Resonance Imaging, Male, Pancreatitis, Recurrence, Retrospective Studies, Tomography, X-Ray Computed}, issn = {1502-7708}, doi = {10.3109/00365521.2012.729084}, author = {Minen, Federico and De Cunto, Angela and Martelossi, Stefano and Ventura, Alessandro} } @article {1873, title = {Acute febrile cholestatic jaundice in children: keep in mind Kawasaki disease.}, journal = {J Pediatr Gastroenterol Nutr}, volume = {55}, year = {2012}, month = {2012 Oct}, pages = {380-3}, abstract = {

Kawasaki disease (KD) is characterized by persistent fever in addition to 4 of 5 signs of mucocutaneous inflammation. Although gastrointestinal involvement does not belong to the classic diagnostic criteria, it has been often associated with KD onset. We reviewed patients who were admitted for febrile cholestatic jaundice between 2003 and 2010 in 2 tertiary pediatric care centers. KD was the second most frequent cause (21\%) after viral infections. Considering the relative high frequency of this condition, a high index of suspicion of KD should be maintained in patients presenting with febrile cholestatic jaundice.

}, keywords = {Child, Child, Preschool, Diagnosis, Differential, Female, Fever, Humans, Infant, Jaundice, Obstructive, Male, Mucocutaneous Lymph Node Syndrome, Virus Diseases}, issn = {1536-4801}, doi = {10.1097/MPG.0b013e31825513de}, author = {Taddio, Andrea and Pellegrin, Maria Chiara and Centenari, Chiara and Filippeschi, Irene Pellegrini and Ventura, Alessandro and Maggiore, Giuseppe} } @article {1798, title = {Association between BclI polymorphism in the NR3C1 gene and in vitro individual variations in lymphocyte responses to methylprednisolone.}, journal = {Br J Clin Pharmacol}, volume = {73}, year = {2012}, month = {2012 Apr}, pages = {651-5}, abstract = {

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In vitro lymphocyte steroid sensitivity has been suggested as a useful tool to predict in vivo response to glucocorticoid treatment in different inflammatory chronic diseases. A correlation between genetic polymorphisms and clinical response to glucocorticoids has been demonstrated in these patients.

WHAT THIS STUDY ADDS: The BclI polymorphism in the glucocorticoid receptor (NR3C1) gene is associated with higher methylprednisolone potency in vitro. The combined evaluation of the in vitro sensitivity to methylprednisolone and BclI polymorphism could represent an aid for physicians to adjust therapy a priori. AIM To evaluate the association between the in vitro sensitivity of peripheral blood mononuclear cells (PBMCs) to methylprednisolone (MP) and the presence of genetic polymorphisms involved in glucocorticoid (GC) response.

METHODS: In vitro MP inhibition of the proliferation of lymphocytes stimulated with concanavalin A was determined. Non linear regression of dose-response data was performed computing the MP concentration required to reduce proliferation to 50\% (IC(50) ). The maximum inhibition achievable at the highest MP concentration (I(max) ) was also calculated. Moreover, the Taqman technique was used to analyze the BclI polymorphism in the NR3C1 gene and the Leu155His polymorphism in the NALP1 gene.

RESULTS: A significant association between the BclI mutated genotype and an increased in vitro sensitivity to GCs was observed.

CONCLUSIONS: The a priori evaluation of the BclI polymorphism, associated with a lymphocyte proliferation assay, could represent a useful diagnostic tool for the optimization of steroid treatment.

}, keywords = {Adaptor Proteins, Signal Transducing, Adolescent, Adult, Apoptosis Regulatory Proteins, Cyclin D1, Dose-Response Relationship, Drug, Female, Genotype, Glucocorticoids, Humans, Lymphocytes, Male, Methylprednisolone, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Glucocorticoid, Young Adult}, issn = {1365-2125}, doi = {10.1111/j.1365-2125.2011.04130.x}, author = {Cuzzoni, Eva and De Iudicibus, Sara and Bartoli, Fiora and Ventura, Alessandro and Decorti, Giuliana} } @article {1794, title = {Ages of celiac disease: from changing environment to improved diagnostics.}, journal = {World J Gastroenterol}, volume = {17}, year = {2011}, month = {2011 Aug 28}, pages = {3665-71}, abstract = {

From the time of Gee{\textquoteright}s landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.

}, keywords = {Autoantibodies, Celiac Disease, Diet, Gluten-Free, Gliadin, Glutens, History, 19th Century, History, 20th Century, History, 21st Century, History, Ancient, History, Medieval, Humans, Transglutaminases}, issn = {2219-2840}, doi = {10.3748/wjg.v17.i32.3665}, author = {Tommasini, Alberto and Not, Tarcisio and Ventura, Alessandro} } @article {1626, title = {Anti transglutaminase antibodies cause ataxia in mice.}, journal = {PLoS One}, volume = {5}, year = {2010}, month = {2010}, pages = {e9698}, abstract = {

BACKGROUND: Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.

METHODS: We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75\% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.

CONCLUSION: The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.

}, keywords = {Adult, Animals, Antibodies, Ataxia, Autoimmune Diseases, Brain, Celiac Disease, Female, Gliadin, Humans, Isoenzymes, Male, Mice, Mice, Inbred C57BL, Middle Aged, Motor Skills, Rats, Rats, Sprague-Dawley, Transglutaminases}, issn = {1932-6203}, doi = {10.1371/journal.pone.0009698}, author = {Boscolo, Sabrina and Lorenzon, Andrea and Sblattero, Daniele and Florian, Fiorella and Stebel, Marco and Marzari, Roberto and Not, Tarcisio and Aeschlimann, Daniel and Ventura, Alessandro and Hadjivassiliou, Marios and Tongiorgi, Enrico} }