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Celiac.com 10/06/2023 - Typically, treating autoimmune diseases involves broad immunosuppression, which has various side effects. However, a team of researchers have developed a novel approach to suppress established antigen-specific immune responses without the need for global immunosuppression. The research team includes Andrew C. Tremain, Rachel P. Wallace, Kristen M. Lorentz, Thomas B. Thornley, Jennifer T. Antane, Michal R. Raczy, Joseph W. Reda, Aaron T. Alpar, Anna J. Slezak, Elyse A. Watkins, Chitavi D. Maulloo, Erica Budina, Ani Solanki, Mindy Nguyen, David J. Bischoff, Jamie L. Harrington, Rabinarayan Mishra, Gregory P. Conley, Romain Marlin, Nathalie Dereuddre-Bosquet, Anne-Sophie Gallouët, Roger LeGrand, D. Scott Wilson, Stephan Kontos, and Jeffrey A. Hubbell. They are variously affiliated with the Committee on Immunology, University of Chicago, Chicago, IL, USA; the Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA; the Committee on Cancer Biology, University of Chicago, Chicago, IL, USA; the Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; the Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France; the Animal Resources Center, University of Chicago, Chicago, IL, USA; and with Anokion US Inc., Cambridge, MA, USA. Their study introduces a new method using a polymer glycosylated with N-acetylgalactosamine (pGal) that is conjugated to the antigen. This approach enables the dissociation of the antigen upon endocytosis, allowing it to be presented in an immunoregulatory environment. The research demonstrates that pGal–antigen therapy can induce antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis, driven by the programmed cell-death-1 pathway and the co-inhibitory ligand CD276. Moreover, this therapy effectively suppresses antigen-specific responses in non-human primates vaccinated against a DNA-based simian immunodeficiency virus. In essence, pGal–antigen therapy offers a promising avenue for addressing autoimmune diseases by specifically targeting and resolving antigen-specific inflammatory T-cell responses. In the future, this approach could be applied to various autoimmune diseases, possibly even celiac disease, offering a more precise and effective alternative to current treatments that rely on broader immunosuppression. Read more in Nature Biomedical Engineering

Celiac.com 05/12/2022 - Recent studies suggest that KIR+CD8+ T cells could offer a path to controlling autoimmune diseases, such as “long COVID,” which emerge after viral infections. Ly49+CD8+ T cells are a subset of CD8+ T cells that have shown immunoregulatory activity in mice. These cells can suppress myelin oligodendrocyte glycoprotein (MOG)–specific pathogenic CD4+ T cells through their cytolytic activity and thereby ameliorate experimental autoimmune encephalomyelitis (EAE). However, whether a similar CD8+ regulatory T cell subset exists in humans and whether its suppressive activity extends beyond autoimmune diseases to play a more general role in peripheral tolerance remains to be determined. A team of researchers recently shared some relevant findings regarding CD8+ T cells in humans. The research team included Jing Li; Maxim Zaslavsky; Yapeng Su; Jing Guo; Michael J Sikora; Vincent van Unen; Asbjørn Christophersen; Shin-Heng Chiou; Liang Chen; Jiefu Li; Xuhuai Ji; Julie Wilhelmy; Alana M McSween; Brad A Palanski; Venkata Vamsee Aditya Mallajosyula; Nathan A Bracey; Gopal Krishna R Dhondalay; Kartik Bhamidipati; Joy Pai; Lucas B Kipp; Jeffrey E Dunn; Stephen L Hauser; Jorge R Oksenberg; Ansuman T Satpathy; William H Robinson; Cornelia L Dekker; Lars M Steinmetz; Chaitan Khosla; Paul J Utz; Ludvig M Sollid; Yueh-Hsiu Chien; James R Heath; Nielsen Q Fernandez-Becker; Kari C Nadeau; Naresha Saligrama; and Mark M Davis. A recent report by Li et al., notes the existence of a similar CD8+ T cell subset in humans, which possess killer cell immunoglobulin-like receptors (KIRs). This function in humans mirrors that in the mouse Ly49 family. These cells are able to suppress self-reactive CD4+ T cells, and are more plentiful in patients with autoimmune conditions, such as celiac disease, multiple sclerosis, and lupus, as well as in patients infected with influenza virus or severe acute respiratory syndrome coronavirus 2. When researchers injected viruses into mice selectively deficient in Ly49+CD8+ T cells, the mice showed normal antiviral immune responses, but they later developed symptoms of autoimmune disease. The team found that CD8+ T cells express inhibitory killer cell immunoglobulin-like receptors (KIRs), making them the human equivalent of Ly49+CD8+ regulatory T cells in mice. These CD8+ T cells are abundant in the blood and inflamed tissues of patients with several different autoimmune diseases. Moreover, these CD8+ T cells easily eliminated pathogenic gliadin-specific CD4+ T cells from the leukocytes of celiac disease patients in vitro. Because of this, KIR+CD8+ T cells could offer a path to controlling autoimmune diseases, such as “long COVID,” which emerge after viral infections. Tellingly, in COVID-19 patients, the team also found elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, which corresponded to disease severity, and levels of vasculitis. Selective destruction of Ly49+CD8+ T cells in virus-infected mice reversed their infections, and restored their autoimmunity. These results suggest that in humans, as in mice, these regulatory CD8+ T cells act uniquely to suppress pathogenic T cells in autoimmune and infectious diseases. Read more in Science. 2022 Apr 15;376(6590):eabi9591. Also: PubMed. The researchers are variously affiliated with the Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA; the Program in Computer Science, Stanford University, Stanford, CA, USA; the Institute for Systems Biology, Seattle, WA, USA; the Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; the Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; the KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway; the Institute of Clinical Medicine, University of Oslo, Oslo, Norway; the Department of Immunology, University of Oslo, Oslo, Norway; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA; the Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA; the Department of Chemistry, Stanford University, Stanford, CA, USA; Sean N; Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Stanford, CA, USA; the Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; the Department of Neurology and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA; the Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA; the Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; the Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA; the European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany; the Department of Chemical Engineering, Stanford University, Stanford, CA, USA; the Stanford ChEM-H, Stanford University, Stanford, CA, USA; the Department of Immunology, Oslo University Hospital, Oslo, Norway; the Department of Bioengineering, University of Washington, Seattle, WA, USA; and the Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.

Celiac.com 01/17/2022 - People with autoimmune disorders face an elevated risk for celiac disease, but there's no clear data to show exactly how high that risk might be. To clarify the issue, a team of researchers recently set out to assess the incidence of autoimmune disorders in treated patients with celiac disease. The research team included Muhammad R. Khan; Shilpa S. Nellikkal; Ahmed Barazi; Joseph J. Larson; Joseph A. Murray; and Imad Absah. They are variously affiliated with the Division of Pediatric Gastroenterology and Hepatology; the Division of Biomedical Statistics and Informatics; and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. The team used the Rochester Epidemiology Project to conduct a retrospective medical record search for patients diagnosed with celiac disease at the Mayo Clinic's Olmsted Medical Center from January 1997 to December 2015. For each patient with celiac disease, the team assigned two non-celiac control subjects matched for age and sex during the study period. They used Kaplan-Meier analysis to determine the incidence rate of autoimmune disorder diagnosis five years after index date, for the celiac disease cases and controls. They then compared the results using the log-rank test. They found nearly 250 treated patients with celiac disease during the study period, matched to just under 500 matched control subjects. About one third of patients were boys. Within five years of the index date, 5.0% of celiac patients had a new autoimmune disorder diagnosis, compared with 1.3% of non-celiac control subjects. In the presence of a prior autoimmune disorder, the celiac disease group faced a much higher cumulative risk of a new or additional autoimmune disorder compared with control subjects. The data show that treated patients with celiac disease face a higher risk of developing autoimmune disorders than non-celiacs. The risk of a new autoimmune disorder is significantly higher in children, especially those with an existing autoimmune disorder. Read more: Journal of Pediatric Gastroenterology and Nutrition, October 2019 - Volume 69 - Issue 4 - p 438-442

Celiac.com 11/10/2020 - Around 1 in 100 people have celiac disease, making it one of the more common (yet under diagnosed) autoimmune disorders in the world. This illness can have a huge impact on a person’s quality of life and often results in other detrimental knock-on effects, such as stress and anxiety. For those people who struggle with a chronic illness, invisible or otherwise, practicing meditation can offer huge rewards for both body and mind. The Effects of Celiac Disease on Everyday Life For those suffering from celiac disease, the effects of their illness can be uncomfortable at best and debilitating at worst. As opposed to gluten sensitivity, from which people may only experience more mild symptoms, celiac disease is an autoimmune disorder which can ultimately lead to malnutrition and other serious health problems. There is no known cure for celiac disease; instead, people must just try to follow a strict gluten-free diet to minimize the symptoms and prevent any long term complications. The impact of this disease on daily life cannot be underestimated: those suffering with celiac disease can live in constant fear of food, with the continual need to check food labels and plan meals in advance, coupled with the perpetual worry of visiting restaurants with friends for fear of getting sick. All this can take an enormous strain on the person’s health and wellbeing—not just physically of course, but also emotionally and mentally. This isn’t to say, of course, that people with celiac disease can’t lead a happy and healthy life—they simply encounter more challenges in doing so. One such challenge is learning how to manage the stress and anxiety of living with a chronic condition, and protecting their wellbeing in a sustainable and holistic way. The Link Between Celiac Disease and Stress Stress, which has been classified as “the health epidemic of the 21st century” by the World Health Organization and can be experienced as a result of celiac disease, can actually contribute towards making an autoimmune disease even worse than it already is. It has long been established that stress is a key factor in the experience of many illnesses, and appears to have an especial impact on those with chronic conditions. This is because when we feel intensely stressed, we can experience symptoms that are extremely similar to the symptoms of celiac disease (such as fatigue and digestive issues), exacerbating an already difficult situation and triggering fear that we will suffer from a flare up. Some people even believe that their celiac disease was triggered by a stressful life event, such as divorce, and may find their body is less cooperative when they anxious and unhappy. This vicious cycle of stress, intensified symptoms and more stress can feel like an inevitable, exhausting loop which a person suffering with the disease may never see themselves breaking from. There is a way to help the situation though—through the practice of meditation. How Can Meditation Help? Meditation is an invaluable tool that can be used to help ease the stress of living with celiac disease. While there needs to be more research, some consider meditation to be a completely natural way to regulate our immune system (and evidence certainly does suggest it improves immune function). It also provides a wealth of other scientifically-backed health benefits, along with being hugely helpful in dealing with stress. We only need to practice for 20 minutes a day to be able to see the results, so long as we make the time to do so on a regular basis (every day is best). A simple mantra-based meditation we can try requires us to repeat the word “beeja’ over and over in our minds whilst trying to quiet the noise of other thoughts. By focusing on this one word, we train our brain to connect the mind and body, and be present in the moment without worrying about other things happening in the past or future. The significant restorative effects of meditation can bring harmony between our body, mind and nervous system—thereby providing our body with the opportunity to reset and rest on a profound level. During meditation, our levels of rest and stillness are so deep that our brain is able to rewire itself to provide a more balanced and adaptive response to the challenges we face. Brain imaging technology suggests that just 3 months of meditation shrinks the amygdala (a.k.a the “stress center”) and boosts our grey matter, making us both calmer and more mentally resilient. This is particularly beneficial for those suffering from the stress that living with a chronic condition can cause, as the ‘fight and flight’ response is no longer so easily triggered. The experience of stress, and the fear of flare ups, is a common issue for those living with celiac disease, so learning ways to dissipate stress naturally can be genuinely life-changing. Anecdotally, many people find meditation eases the symptoms of autoimmune disorders, and it is theorized that the time spent meditating (plus the relaxed state of being that follows a meditative session), soothes an over reactive immune response so our body is more able to distinguish the difference between what might harm us and what won’t. Furthermore, if we can control stress through meditation, then we can certainly consider it as an anti-inflammatory exercise. Meditation using mantras can help us to manage our stress response, so that our immune system becomes less hyperactive, and has the potential to reduce symptoms of inflammation and discomfort. Conclusion If you suffer with an invisible chronic illness, such as celiac disease, then meditation can help you to remain naturally optimistic, and approach your physical and mental health with a practice that provides relief from stress, anxiety and depression—therefore equipping you with the tools to better cope with your autoimmune illness. Think of it as a self-care ritual—you can even just do it whilst you’re waiting for the kettle to boil—and view it as a daily healing practice rather than a destination towards which you must strive. The journey will be well worth it.

Celiac.com 10/23/2019 - Autoimmune therapy company ImmunoMolecular Therapeutics (IM Therapeutics) has received $10 million in Series A financing to support its new HLA-targeted treatment approach to autoimmune diseases, and to develop its lead HLA-targeted drug candidate for type 1 diabetes. Founded by physician scientists at the University of Colorado's Barbara Davis Center for Diabetes, IM Therapeutic creates personalized therapies for autoimmune diseases. The company's research has shown that blocking certain high risk human leukocyte antigen (HLA) genes also blocks the subsequent autoimmune response, which offers a possible way to prevent autoimmune triggering in a number of autoimmune diseases. Based on that research, the company is creating personalized therapies against HLA targets in various autoimmune diseases, including type 1 diabetes and celiac disease. The company has clinically proven that treating patients based on HLA-DQ8 status can reduce the autoimmune response in type 1 diabetes. With a technology platform that integrates computational chemistry, bioassays, and rational drug design, IM Therapeutics is developing a series of HLA targets for a number of autoimmune diseases. IM Therapeutics' personalized therapy approach to treating autoimmune disorders has proven effective in a Phase 1b human study of recently diagnosed type 1 diabetes patients who were positive for the HLA DQ8 variant. The Company is moving forward on its lead oral drug, IMT-002, through IND development for type 1 diabetes, and expanding its therapeutic HLA blocking treatments to other targets of autoimmune disorders, including celiac disease. IM Therapeutics’ HLA is currently focused on HLA-DQ8 and DQ2 gene variants, which are known to greatly increase individual risk to both type 1 diabetes and celiac disease. HLA-DQ8 is present in three out of five type 1 diabetes patients, and in one out of ten celiac disease patients. However, about 90% of celiac patients have DQ2, and nearly 100% of celiac patients have DQ2 and/or DQ8. “Our value has been clear since day one – getting to the root cause of autoimmunity with a targeted therapy approach and making an impact on diseases such as type 1 diabetes,” said Nandan Padukone, Ph.D., CEO of IM Therapeutics. Read more at Businesswire.com