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Autoimmune Enterocolitis

Laëtitia Le Texier, Katie E Lineburg, Benjamin Cao, Cameron McDonald-Hyman, Lucie Leveque-El Mouttie, Jemma Nicholls, Michelle Melino, Blessy C Nalkurthi, Kylie A Alexander, Bianca Teal, Stephen J Blake, Fernando Souza-Fonseca-Guimaraes, Christian R Engwerda, Rachel D Kuns, Steven W Lane, Michele Teng, Charis Teh, Daniel Gray, Andrew D Clouston, Susan K Nilsson, Bruce R Blazar, Geoffrey R Hill, Kelli P A MacDonald
Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival...
September 22, 2016: JCI Insight
Carlo Caffarelli, Francesca Santamaria, Dora Di Mauro, Carla Mastrorilli, Virginia Mirra, Sergio Bernasconi
This review focuses key advances in different pediatric fields that were published in Italian Journal of Pediatrics and in international journals in 2015. Weaning studies continue to show promise for preventing food allergy. New diagnostic tools are available for identifying the allergic origin of allergic-like symptoms. Advances have been reported in obesity, short stature and autoimmune endocrine disorders. New molecules are offered to reduce weight gain and insulin-resistance in obese children. Regional investigations may provide suggestions for preventing short stature...
August 27, 2016: Italian Journal of Pediatrics
Amy Hsin-Chieh Hsieh, Mutaz Ferman, Michael P Brown, Jane M Andrews
Use of the immune checkpoint inhibitors, ipilimumab and nivolumab, has revolutionised treatment in patients with metastatic melanoma. However, these drugs can cause an autoimmune enterocolitis, with diarrhoea as the presenting symptom. This is conventionally managed by prompt institution of corticosteroid therapy if moderate diarrhoea (3-6 times/day; grade 2) is present for >5 days or if diarrhoea is severe (>6 times/day; grade 3). We report a case of steroid-dependent ipilimumab-induced colitis successfully treated with vedolizumab (an inhibitor of memory T-cell trafficking to the gut), after which complete withdrawal of corticosteroid was achieved...
2016: BMJ Case Reports
Christine Y Louie, Michael A DiMaio, Karen E Matsukuma, Steven E Coutre, Gerald J Berry, Teri A Longacre
Idelalisib is a highly specific small-molecule phosphoinositide-3-kinase δ inhibitor that was recently approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. The known side effects of idelalisib include severe diarrhea and colitis. Here we report the histologic findings in idelalisib-associated enterocolitis in 11 patients with chronic lymphocytic leukemia or follicular lymphoma receiving idelalisib over a 5-year period (2011 to 2015) at our institution...
December 2015: American Journal of Surgical Pathology
Olivier Goulet
The composition of the microbiota varies according to prenatal events, delivery methods, infant feeding, infant care environment, and antibiotic use. Postnatal gut function and immune development are largely influenced by the intestinal microbiota. Emerging evidence has shown that early microbiota colonization may influence the occurrence of later diseases (microbial programming). The vast majority of microbial species (commensals) give rise to symbiotic host-bacterial interactions that are fundamental for human health...
August 2015: Nutrition Reviews
Si Ming Man, Thirumala-Devi Kanneganti
Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto-inflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2 (AIM2)-like receptors (ALR)...
May 2015: Immunological Reviews
M Ganesh, J Pogoriler, J D Goldsmith, V Fox, E Bern
Apoptosis is a histopathologic feature of a few distinct enteropathies including graft versus host disease and autoimmune enteropathy. We describe an unusual case of a neonate who presented on day 1 of life with rectal bleeding and was found to have severe ulceration on colonoscopy with prominent apoptosis on histopathology. The subsequent clinical course was consistent with allergic enterocolitis.
February 11, 2015: Journal of Pediatric Gastroenterology and Nutrition
Angeliki Giannelou, Qing Zhou, Daniel L Kastner
PURPOSE OF REVIEW: Next-generation sequencing is revolutionizing the molecular taxonomy of human disease. Recent studies of patients with unexplained autoinflammatory disorders reveal germline genetic mutations that target important regulators of innate immunity. RECENT FINDINGS: Whole-exome analyses of previously undiagnosed patients have catalyzed the recognition of two new disease genes. First, a phenotypic spectrum, including livedo racemosa, fever with early-onset stroke, polyarteritis nodosa, and Sneddon syndrome, is caused by loss-of-function mutations in cat eye syndrome chromosome region, candidate 1 (CECR1), encoding adenosine deaminase 2...
December 2014: Current Opinion in Allergy and Clinical Immunology
I Varkonyi, E Rakoczi, O Misak, E Komaromi, L Kardos, Z Lampe, Z Szilvassy
We completed a prospective study of 164 patients involved in a Clostridium difficile surveillance programme, evaluating a range of variables such as disease severity, treatment regimen and known clinical risk factors, for their effect on case lethality. The aim of this study was to determine if there are any additional clinical variables worth considering for inclusion in the therapeutic decision-making process. Beyond common risk factors, secondary immunodeficiencies such as diabetes mellitus, malignancy, autoimmune disease, immunosuppressive therapy and chronic hepatitis were assessed...
October 2014: Clinical Microbiology and Infection
Giuseppina Della Vittoria Scarpati, Celeste Fusciello, Francesco Perri, Francesco Sabbatino, Soldano Ferrone, Chiara Carlomagno, Stefano Pepe
Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis...
2014: OncoTargets and Therapy
Jolanta Sarowska, Irena Choroszy-Król, Bożena Regulska-Ilow, Magdalena Frej-Mądrzak, Agnieszka Jama-Kmiecik
The cause of many gastrointestinal diseases, such as irritable bowel syndrome, chronic inflammatory bowel disease: inflammatory and necrotizing enterocolitis or diarrhea: infectious, traveler's diarrhea, and diarrhea caused by antibiotic treatment is an imbalance of intestinal microflora. Probiotics are live microorganisms, which administered in sufficient quantities, have beneficial health effects. The phenomenon of eating probiotic products started 100 years ago, when the first reports showed beneficial effects of probiotic bacteria on human health...
September 2013: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Andrea Lo Vecchio, Mitchell B Cohen
PURPOSE OF REVIEW: The incidence and severity of Clostridium difficile infection (CDI) have increased worldwide in the past two decades. A principal function of the gut microbiota is to protect the intestine against colonization by exogenous pathogens. Increasingly, the gut microbiota have been shown to influence susceptibility to other genetic and environmentally acquired conditions. Transplantation of healthy donor fecal material in patients with CDI may re-establish the normal composition of the gut microbiota and has been shown to be effective in recurrent CDI...
January 2014: Current Opinion in Gastroenterology
Thomas J Borody, Lawrence J Brandt, Sudarshan Paramsothy
PURPOSE OF REVIEW: Faecal microbiota transplantation (FMT) has undergone dramatic progression over the past year and continues to evolve as knowledge of the gastrointestinal microbiota (GiMb) develops. This review summarizes therapeutic advances in FMT, latest FMT therapies and presents the potential of FMT therapeutics in other gastrointestinal and extra-intestinal conditions. RECENT FINDINGS: The GiMb is now known to have a central role in the pathogenesis of many diseases...
January 2014: Current Opinion in Gastroenterology
Loek P Smits, Kristien E C Bouter, Willem M de Vos, Thomas J Borody, Max Nieuwdorp
There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases...
November 2013: Gastroenterology
Eitan Israeli, Yehuda Shoenfeld
Clostridium difficile is the etiologic agent of nosocomial and community-acquired diarrhea associated with exposure to antibiotics that disrupt the normal colonic flora. As antibacterials currently used for primary C. difficile infections favor recurrences, new methods able to neutralize the bacterium without affecting the gut microbiota are badly needed. Complementary treatment with probiotic agents to reconstitute the physiologicaL intestinal flora does not yield any consistent benefit. In recent years, fecal transplantation has been used in the English-speaking countries with cure rates of about 87%...
April 2013: Harefuah
Helieh S Oz, Theresa Chen, Willem J S de Villiers
BACKGROUND: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection...
2013: Frontiers in Immunology
Dana M H Dykes, Sean R Moore, D Brent Polk, Michael J Rosen, Marcia L Wills, Brian Morris, Jeanine S Maclin, Janaina Nogueira, Avi Katz, Tracey E Hunley, Judith Pugh, Shehzad Saeed
Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as "MMF-related enterocolitis," has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients...
2012: Case Reports in Pediatrics
Monica Viladomiu, Raquel Hontecillas, Mireia Pedragosa, Adria Carbo, Stefan Hoops, Pawel Michalak, Katarzyna Michalak, Richard L Guerrant, James K Roche, Cirle A Warren, Josep Bassaganya-Riera
Clostridium difficile is an anaerobic bacterium that has re-emerged as a facultative pathogen and can cause nosocomial diarrhea, colitis or even death. Peroxisome proliferator-activated receptor (PPAR) γ has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile and its toxins remains largely unknown. To characterize the role of PPARγ in C. difficile-associated disease (CDAD), immunity and gut pathology, we used a mouse model of C...
2012: PloS One
Olga C Aroniadis, Lawrence J Brandt
PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) re-establishes a balanced intestinal flora with resultant cure of recurrent Clostridium difficile infection (RCDI). FMT has also been used to treat other gastrointestinal (GI) diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation and a variety of non-GI disorders. The purpose of this review is to discuss the intestinal microbiota and FMT treatment of GI and non-GI diseases...
January 2013: Current Opinion in Gastroenterology
U Daniluk, M Alifier, M Kaczmarski
In this short review we attempt to establish and/or strengthen connections between probiotics administration and apoptotic pathway in gastrointestinal tract. The disturbance of apoptosis is mainly deliberated in the framework of insufficient removal of immuno-effector cells that may cause autoimmunity. In the context of the inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC), the commensal bacteria and their products effect on gut and immune cell survival are illustrated. The multitude of mechanisms of probiotics to induce cell death is shortly summarized and some aspects of it are being discussed in greater detail...
2012: Advances in Medical Sciences
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