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Jefferson Adams posted a topic in Publications & PublicityView full article
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 01/23/2019 - In the last decade or so, researchers have learned a great deal about the nature of celiac disease. They have learned that celiac disease can arise at any age, that it can have a myriad of symptoms, or no symptoms at all, and that proper diagnosis and treatment is key to avoiding serious complications later on in life. The researchers note that the Oslo definitions establish consensus on celiac disease terminology, but they offer no phenotypic classification for making a composite celiac diagnosis. A team of researchers recently set out to develop a simple phenotypic classification for celiac disease. The research team included Ajit Sood, Vandana Midha, Govind Makharia, B. K. Thelma, Shivalingappa S Halli, Varun Mehta, Ramit Mahajan, Vikram Narang, Kriti Sood, and Kirandeep Kaur. The team established several factors important for phenotypic classification, including age at diagnosis, age at symptom onset, clinical features, family history, and complications, and they applied these factors to 1,664 patients listed in an existing registry at Dayanand Medical College and Hospital, Ludhiana, India. The researchers evaluated patients below age 15, and below age 18 years, and verified their classifications by using cross tabulations of the existing data. For validation of their process and the results the team solicited review by recognized experts from numerous disciplines. Form these results, the research team concludes that their APC classification process, based on age at diagnosis, presentation, complications, offers a simple disease explanatory classification for patients with celiac disease, and can help to provide a composite diagnosis. It’s exciting to know that the answers to three simple questions can help doctors to diagnose celiac disease. Stay tuned for more on this and other stories. Source: Intest Res. DOI: https://doi.org/10.5217/ir.2018.16.2.288 The researchers are variously affiliated with the Department of Gastroenterology, Dayanand Medical College in Ludhiana, India; the Department of Internal Medicine, Dayanand Medical College, Ludhiana, India; the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences in New Delhi, India; the Department of Genetics, University of Delhi South Campus in New Delhi, India; the Department of Community Health Sciences, Faculty of Medicine, University of Manitoba in Winnipeg, Canada; the Department of Pathology, Dayanand Medical College, Ludhiana, India; and the Department of Pharmacology, Dayanand Medical College in Ludhiana, India.
Structure-Based Selection of Small Molecules to Alter Allele-Specific MHC Class II Antigen Presentation
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.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/â€‹jimmunol.1100746