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Found 5 results

  1. Celiac.com 10/18/2018 - A team of researchers recently set out to investigate the prevalence of human leukocyte antigens (HLA) DQ2 and DQ8 haplotypes, two common polymorphisms associate with celiac disease, in women who have had previous stillbirth, but who do not have celiac disease. The research team included Mauro Cozzolino, Caterina Serena, Antonino Salvatore Calabró, Elena Savi Marianna, Pina Rambaldi, Serena Simeone, and Serena Ottanelli, Giorgio Mello, Giovanni Rombolá, Gianmarco Troiano, Nicola Nante, Silvia Vannuccini, Federico Mecacci, and Felice Petraglia. They are variously affiliated with the Division of Obstetrics and Gynecology, and the Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, at Careggi University Hospital, University of Florence in Florence, Italy. For their study, the team enrolled 56 women with history of unexplained term stillbirth referred to our Center for High‐Risk Pregnancies for a preconception counseling. As a control group, they enrolled 379 women with previous uncomplicated pregnancies. They excluded women with celiac women from the study. The team then conducted genetic tests for HLA DQ2/DQ8 on both groups, and compared patients data against controls. They found that 50% of women with history of unexplained term stillbirth tested positive for HLA‐DQ2 or DQ8, compared with just 29.5% for controls. Women with HLA DQ8 genotype showed a substantially higher risk of stillbirth (OR: 2.84 CI: 1.1840‐6.817). For patients with the DQ2 genotype, the OR for stillbirth was even higher, at 4.46 with a CI of 2.408‐8.270. In the stillbirth group, the team found that SGA neonates in 85.7% those with HLA‐DQ2/DQ8 haplotypes, and in just 42.8% with negative genetic testing. The team found significantly higher rates of HLA DQ2/DQ8 haplotypes in women with history of unexplained term stillbirth than in women with previous uneventful pregnancies. Moreover, they found that HLA DQ2/DQ8 positivity was significantly associated with suboptimal fetal growth in intrauterine fetal death cases, as shown by an increased prevalence of SGA babies. This study will definitely be of interest to women with HLA DQ2/DQ8 haplotypes, and to those who have experienced unexplained stillbirths. Stay tuned for more information on this important topic as news becomes available. Read more at: American Journal of Reproductive Immunology
  2. Celiac.com 02/05/2018 - TIMP-GLIA, a new nanoparticle-based celiac disease treatment currently under development by Cour Pharmaceuticals, has received Fast Track Designation from the US Food and Drug Administration (FDA). Phase 1 studies to assess the safety and tolerability of TIMP-GLIA are currently underway in the United States. TIMP-GLIA works in part by encapsulating a component of wheat within a nanoparticle. The treatment has resulted in gluten tolerance in numerous animal models. By encasing components of gluten proteins in a nanoparticle, Cour is hoping that the gluten will remain unrecognized by the body's immune system, at least until immune tolerance can be generated through non-inflammatory antigen presentation. The FDA created the fast track process to speed development, review and commercialization of drugs that target serious conditions and fill an unmet medical need. Fast Track Designation puts Cour in a "prime position to advance an innovative new approach for the treatment of Celiac Disease," said John J. Puisis, CEO of Cour Pharmaceuticals. Cour is investigating TIMP-GLIA as part of an effort to reprogram the body's immune system so patients develop a tolerance to gluten as a non-threatening substance and ultimately to reduce or reverse celiac disease without the need for immune suppressing drugs. Cour's approach is designed to work by encasing a component of wheat in a nanoparticle, and introducing that particle into a celiac disease patient. If it works as designed, the gluten will remain unrecognized by the body's immune system until tolerance can be achieved through non-inflammatory antigen presentation. The phase 1 clinical trial for TIMP-GLIA study is being conducted at centers in the United States. The objective of the study is to assess the safety and tolerability of TIMP-GLIA when administered intravenously (IV) as a single dose at ascending dose levels and as a repeat dose in subjects with celiac disease. All in all, this is another of many bold and encouraging efforts to treat or cure celiac disease that have arisen in the last few years. Look for news of success or failure over then next few years. Source: Pharmabiz.com
  3. Celiac.com 08/10/2015 - The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but its usefulness for screening is still uncertain. A research team recently set out to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. The research team included A. Díaz-Redondo, J. Miranda-Bautista, J. García-Lledó, J.P. Gisbert, and L. Menchén. They are variously affiliated with the Hospital General Universitario Gregorio Marañón in Madrid, Spain, and with the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Madrid, Spain. The team conducted a systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease. They searched MEDLINE and EMBASE for the period running from 1st January 2004 until 31st December 2013 and used two independent researchers to carry out selection and classification of studies, data extraction and analysis. The team conducted meta-analysis that combined sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease and ended up with six studies that included a total of 1303 people. The results showed pooled sensitivity at 98%, with 95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48). Regarding specificity, studies were heterogeneous and a the team ran a subgroup analysis according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09). Because it offers high sensitivity and low negative likelihood ratio, the team concludes that human leukocyte antigen-DQ2/DQ8 typing makes an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population. Source: Rev Esp Enferm Dig. 2015 Jul;107(7):423-429.
  4. Celiac.com 06/17/2013 - To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease, a team of researchers recently looked at human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases. The research team included Daniel DiGiacomo, Antonella Santonicola, Fabiana Zingone, Edoardo Troncone, Maria Cristina Caria, Patrizia Borgheresi, Gianpaolo Parrilli, and Carolina Ciacci. They are variously affiliated with the Gastrointestinal Unit of University Federico â…¡ in Naples, Italy, the Department of Medicine, Celiac Disease Center of Columbia University in New York, in the United States, The Celiac Center of Loreto Crispi Hospital in Naples, Italy, the Celiac Center, Gastrointestinal Unit in San Giovanni di Dio e Ruggi d’Aragona Hospital at the University of Salerno, and the Department of Medicine and Surgery, Campus di Baronissi at the University of Salerno Medical School in Baronissi, Italy. The team assessed HLA DQ2/8 status in 443 patients from three ambulatory gastroenterology clinics in Southern Italy. The clinics were located at the University of Federico â…¡ and Loreto Crispi Hospital in Naples, and Ruggi D’Aragona Hospital in Salerno. The team grouped patients according disease status for pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), along with DQ2/8 alleles, which correspond to a celiac disease genetic risk scale. They then compared allele frequencies in the test subjects with healthy Italian control subjects. Out of 443 subjects, the team found that 196 subjects (44.2%), tested positive for DQ2/8. The average age of DQ2/8 positive subjects was 56 years, and 42.6% were female. Overall, the team found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Moreover, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Additionally, people with functional upper GI diseases disorders had rates of DQ2/8 positivity that were nearly double those of healthy control subjects. Those with liver disease had rates of DQ2/8 positivity that were 1.3 percent higher than controls, though this rate is not statistically significant. People with IBS and IBD had a lower rates of DQ2/8 positivity compared to healthy controls. Compared to general population estimates, the percentage of individuals who were HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD. Source: World J Gastroenterol 2013 April 28; 19(16): 2507-2513. ISSN 1007-9327 (print) ISSN 2219-2840 (online). doi:10.3748/wjg.v19.i16.2507
  5. Celiac.com 12/05/2011 - Class II major histocompatibility molecules are one of the main points of susceptibility for a number of autoimmune disorders, including type 1 diabetes. A team of researchers recently set out to investigate structure-based selection of small molecules to alter allele-specific MHC Class II antigen presentation The research team included Aaron W. Michels, David A. Ostrov, Li Zhang, Maki Nakayama, Masanori Fuse, Kristen McDaniel, Bart O. Roep, Peter A. Gottlieb, Mark A. Atkinson, and George S. Eisenbarth. They are variously affiliated with the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, in Gainesville, FL, and with the Department of Immunohaematology and Blood Transfusion at Leiden University Medical Center in Leiden, The Netherlands. In the NOD mouse model of spontaneous autoimmune diabetes, Human DQ8 and I-Ag7 imparts diabetes risk by modulating presentation of specific islet peptides in the thymus and surrounding area. To define small molecules that could live in specific structural pockets along the I-Ag7 binding groove, the research team made use of an in-silico molecular docking program to review a vast “drug-like” chemical library. They were hoping to either promote or inhibit presentation to T cells of the autoantigen insulin B chain peptide, which consists of amino acids 9–23. By making use of both murine and human cells, the team's results show that small molecules can in fact influence specific TCR signals in the presence of cognate target peptides, based upon the targeted structural pocket. The effect of a compound on TCR response varied among targeted pockets, with pocket 1 and 6 compounds inhibiting TCR response, and molecules targeted at pocket 9 promoting peptide responses. It takes just nanomolar levels of the inhibitory molecules to block the insulin B chain peptide, which consists of amino acids 9–23, endogenous insulin, and islet-stimulated T cell responses. At concentrations as low as 10 nM, Glyphosine, a pocket 9 compound, enhances insulin peptide presentation to T cells, upregulates IL-10 secretion, and prevents diabetes in NOD mice. These studies offer a new way to identify small molecules that can both stimulate and inhibit T cell responses, thus offering a potential for future therapeutic treatment options. Source: Journal of Immunology doi: 10.4049/​jimmunol.1100746
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