Latest news with #celiacdisease
Medscape
28-05-2025
- Health
- Medscape
Bone Metabolism in Celiac Disease
When most people think of celiac disease (CD), they understandably associate it with digestive system problems such as bloating, diarrhea, and abdominal pain. The chronic autoimmune disorder, characterized by an abnormal immune response to gluten — a protein found in wheat, barley, and rye— leads to damage of the small intestine when people with the disorder consume gluten. This intestinal damage causes uncomfortable digestive symptoms associated with the disease, but it also affects a very different system: the skeletal system. This is because CD impairs absorption of essential nutrients, including calcium and vitamin D — two nutrients crucial for maintaining bone health. As a result, individuals with CD are at an increased risk for developing metabolic bone diseases, such as osteomalacia, low bone density, and osteoporosis. Thus, prompt diagnosis of the condition, which affects approximately 1%-2% of the global population, is crucial in order to prevent these bone consequences. This also highlights the need for bone screening in those found to have the disease. Importantly, a significant number of patients with CD may present without the classic gastrointestinal symptoms, instead exhibiting extraintestinal manifestations, including bone loss. An impact on bone health has been reported in individuals with CD across a range of ages, including children. Postmenopausal women with the condition are at heightened risk due to associated estrogen deficiency, which further compromises bone density. Older adults with CD are also more vulnerable as bone mass naturally declines with age and is further exacerbated by malabsorption-related deficiencies. Regional studies indicate that the prevalence of CD-associated osteoporosis is particularly high in Europe and North America. A Danish study reported that the risk of major osteoporotic fractures is increased by 37% and of any fractures by 27% in patients with CD. The pathophysiology of bone disease in CD is multifactorial. The intestinal damage caused by the condition results in the malabsorption of vitamin D, which plays an essential role in calcium and phosphate homeostasis and in promoting optimal conditions for bone mineralization. Vitamin D deficiency is common in untreated CD and drives bone loss and can cause osteomalacia — a condition characterized by softening of bones. In children with CD, severe vitamin D deficiency with reduction in phosphate levels can cause rickets. Further, impaired calcium absorption and hypocalcemia triggers secondary hyperparathyroidism— a compensatory increase in parathyroid hormone (PTH) secretion aimed at restoring serum calcium levels. PTH stimulates osteoclast activity, leading to increased bone resorption and, ultimately, a deterioration in bone microarchitecture. Thus, bone impairment may occur even when serum calcium levels appear normal. Systemic inflammation also plays a critical role. Pro-inflammatory cytokines such as TNF-alpha and IL-1 and -6 are elevated in CD and are known to directly stimulate osteoclastogenesis. These cytokines promote bone resorption and interfere with bone formation, further skewing the balance toward bone loss. Hormonal disturbances may contribute to bone disease in CD. Women with CD may experience menstrual irregularities, such as amenorrhea or early menopause, resulting in decreased estrogen levels, a hormone critical for bone preservation. In men, a condition of reversible androgen resistance may occur, reducing the anabolic effects of testosterone on bone. Together, these hormonal imbalances can significantly impair bone density. In light of these risks, it is important to promptly screen patients for CD when they have symptoms suggestive of this condition, or in some patients with vitamin D deficiency who do not respond to usual vitamin D replacement doses, or in situations where a diagnosis of low bone density is made for unrelated reasons, to prevent to prevent long-term complications, including bone disease. The preferred initial screening test in patients suspected to have CD and consuming a gluten-containing diet is the tissue transglutaminase IgA antibodies (tTG-IgA) test accompanied by total serum IgA (to rule out IgA deficiency). If IgA concentrations are low, an IgG based test is indicated. A positive serologic test should be followed by endoscopic duodenal biopsy, which can confirm the diagnosis through findings such as increased intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy. However, the biopsy may not be necessary if the tTG-IgA antibody titer is 10 or more times the upper limit of normal. Human leukocyte antigen testing is sometimes necessary in patients with suspected CD. Importantly, diagnostic procedures must be conducted while the patient is still consuming gluten, as high antibody titers and endoscopic findings resolve on a gluten-free diet. The European Society for the Study of Celiac Disease recommends that, upon diagnosis, individuals aged 30-35 or older with CD undergo bone mass density (BMD) testing using dual-energy x-ray absorptiometry (DXA), particularly if there is evidence of malabsorption, if the diagnosis is delayed, or if there are other concerning risk factors for low bone density. DXA scans should be repeated every 5 years if the initial scan was normal, or every 2-3 years if the initial scan revealed low bone density or for ongoing risk factors for low bone density. The American College of Gastroenterology also recommends DXA screening for low bone density in CD. Children with CD, similarly, should be screened with a DXA scan when there are risk factors for low bone density. Calcium, vitamin D, alkaline phosphatase and PTH levels should be checked at diagnosis and monitored annually (or more frequently in the case of children) until they return to normal. The cornerstone of treatment for CD is strict, lifelong adherence to a gluten-free diet (GFD). Eliminating gluten from the diet allows the intestinal mucosa to heal, leading to improved nutrient absorption and a reduction in systemic inflammation. Numerous studies have demonstrated that adherence to a GFD can significantly improve BMD, with notable changes observed within the first year of dietary compliance. The American Gastroenterological Association emphasizes the critical role of the GFD in both gastrointestinal recovery and the prevention of complications like osteoporosis. In addition to the GFD, patients with CD should receive calcium and vitamin D supplementation to address deficiencies and support bone health. The Canadian Family Physician guidelines recommend routine supplementation and monitoring to ensure optimal levels. Regular BMD assessments are advised as previously discussed to detect early signs of bone loss and monitor the effectiveness of interventions. Physical activity, particularly weight-bearing exercises, is encouraged as it helps to stimulate bone formation and enhance skeletal strength. Patients should be encouraged to participate in weight-bearing (bone loading) exercises, resistance training, limit alcohol intake, and avoid cigarette smoking. In severe cases of osteoporosis, antiresorptive medications such as bisphosphonates may be considered. However, evidence supporting their use specifically in CD patients is limited, and such treatments should be tailored to individual needs. Bone disease is a common and potentially serious complication of CD, often arising from a combination of malabsorption, inflammation, and hormonal imbalances. Early detection and comprehensive management — including implementation of a gluten-free diet, nutritional supplementation, and optimal physical activity, along with routine BMD screening — are vital to preserving bone health and preventing long-term complications in individuals with CD.
Yahoo
23-05-2025
- Health
- Yahoo
Experimental Therapy Suppresses Immune Reaction to Gluten in Mice
In a promising new study, scientists have adapted an experimental cancer treatment to control celiac disease. The method successfully quietened the gut's autoimmune reaction in tests using mice, suggesting the treatment could one day become a first-of-its-kind therapy for humans with the condition. For the millions of people with celiac disease, even a small brush with gluten can trigger intestinal nastiness. Immune cells mistake the protein for a threat and launch an attack, leading to diarrhea, pain, and other unpleasant symptoms. A team led by scientists at the University of Lausanne in Switzerland demonstrated a new immunotherapy that seems to quell this overreaction – in mice at least. The researchers engineered regulatory T cells (T regs); a type of immune tissue that calms down the symptom-causing effector T cells. When untreated mice were fed gluten, the effector T cells gathered in the intestines and proliferated, ready for battle. But in mice that had been infused with the engineered T regs, the effector T cells didn't respond to the gluten, and didn't migrate to the gut. The technique is similar to an emerging treatment for cancer called Chimeric Antigen Receptor (CAR) T cell therapy, where immune cells removed from the patient are engineered to better target specific cancer cells before being returned into the body to bolster the defence response. Early results have shown promise against some forms of cancer, although it's not without its own risks. Ironically, using immunotherapy against celiac disease works almost the opposite way to cancer – suppressing immune responses rather than boosting them. In the new study, the team engineered mice to have a particular genetic variation known as HLA-DQ2.5, which the majority of human celiac patients carry. They then developed effector T cells that reacted to gluten, as well as T regs that responded to those effector cells. Both types were then infused into the mice. Interestingly, the mice that received the treatment not only seemed to be protected against the gluten antigen that their effector T cells were primed to attack, but the reaction was also suppressed for immune cells targeting a similar but distinct gluten antigen. Hopes of a functional 'cure' should of course be tamped down for now – there's still a long road before human trials could begin. "Although it looks promising, the study has several limitations," says Cristina Gomez-Casado, an immunologist at the University of Düsseldorf in Germany who was not involved in this research. "1) it only studies the action of T regs against the wheat protein gliadin, so in the future it should be studied if they work against barley and rye proteins; "2) it is not determined when T regs should be used as therapy (before developing the disease or once it has been diagnosed?); "3) the mice used are not celiac, so gluten does not damage their gut, and are only offered once, so the long-term effect of gluten cannot be studied; "4) it is known from other studies that the number of T regs is limited in celiac patients and, in some, they have been found to be non-functional." Future work will need to address these issues, but still, the study lays some intriguing groundwork that could lead to new treatments for celiac disease. Patients could eventually be freed from carefully studying labels and menus, and being punished for days for slight slip-ups. The research was published in the journal Science Translational Medicine. Humans Are Evolving Right in Front of Our Eyes on The Tibetan Plateau Nanoplastics Stick to Toxic Bacteria, Forming a Deadly Combination Expert Explains FDA's New COVID Vaccine Rules in The US
The Guardian
12-05-2025
- Health
- The Guardian
‘Inverse vaccines': the promise of a ‘holy grail' treatment for autoimmune diseases
Autoimmune diseases affect as many as 800 million people around the world – around one in 10 of us. From multiple sclerosis and lupus to type one diabetes and rheumatoid arthritis, these conditions all share a common trait: the body's own immune system turns against itself. Current treatments aim to suppress that response, but dialing down the entire immune system comes at a steep cost: it leaves patients vulnerable to other illnesses and often requires daily, invasive care. A revolution is now underfoot, as researchers are developing a new approach that targets only the specific part of the immune system that's gone rogue. These treatments are known as 'inverse vaccines' because they suppress a particular part of the immune system, rather than amplifying it, as existing vaccines do. 'This is the holy grail,' says Northwestern University immunologist Stephen Miller. 'We want to use a scalpel rather than a sledgehammer to treat these diseases.' Miller's 2021 paper, published in 2022 in Gastroenterology, was the first to demonstrate that inverse vaccines could be effective in humans. The study looked at celiac disease, in which the immune system attacks the intestinal lining when it detects the presence of gluten, a protein found in wheat and other grains. Over two weeks, 33 celiac patients who were in remission ingested gluten; about half had received the inverse vaccine beforehand, while the other half got a placebo. After two weeks, researchers examined the subjects' intestinal lining and found that the inverse vaccine group had no damage, while the placebo group showed a noticeable worsening of symptoms. The basic idea of inverse vaccines rests on using certain synthetic nanoparticles attached to particular disease-related proteins – called antigens – as targeted messengers to retrain the immune system. The nanoparticles mimic dying human cells, a normal ongoing process. Although these dying cells are 'foreign', the immune system knows not to attack them. The immune system learns to ignore both the nanoparticles and the attached proteins, and stops attacking the body. 'What this does is, it re-educates the immune system,' says NYU bioengineer Jeffrey Hubbell. 'So then it says: 'OK, I'm good, I don't need to attack this, because I see that it's not a threat.'' In 2023, Hubbell and his colleagues published a peer-reviewed paper in Nature showing that this method could halt the mouse version of multiple sclerosis (MS), a disease in which the immune system attacks nerve cells in the brain and body. Over the past eight months, Anokion, the company started by Hubbell and others to commercialize their work, has announced successful early trials in humans in both celiac disease and MS. 'There have been more than a few tears of happiness shed by me and my team when we've seen the clinical results,' Hubbell says. The discovery that certain negatively charged molecules could re-train the immune system to stop attacking our own tissues was 'absolute serendipity', says University of Calgary immunologist Pere Santamaria. He was among the first scientists to uncover this. 'I would never have guessed it,' he says. 'Not even in my wildest dreams.' Santamaria has spent most of his career focusing on type one diabetes, a disease in which the immune system attacks the pancreas cells that produce insulin. Recently though, he has begun exploring inverse vaccines for other autoimmune disorders, including a disease called primary biliary cholangitis (PBC) that affects bile ducts in the liver. One advantage of working on PBC is that because it is rare, clinical trials don't require nearly as many patients; as a result, the drug approval process can move more quickly. 'And once we get approval for one indication, we may be able to go faster with others,' Santamaria says. One of the key advantages of inverse vaccines is their broad versatility; it appears that the approach can work for a wide range of autoimmune diseases. 'It works all the time in animals,' says Santamaria. 'We've tried this in many different animal models of autoimmune disease.' (Of course, success in animal studies doesn't automatically translate to success in humans.) Last year, Bana Jabri, the director of Institut Imagine in Paris, cowrote a review of inverse vaccine efforts. She is cautiously optimistic about their potential, but also notes that the immune system is immensely complex. Some immune cells, for example, circulate throughout the body, while others reside permanently in specific tissues. Jabri says it's not yet clear that current inverse immune treatments can affect both kinds of cells. Sign up to Well Actually Practical advice, expert insights and answers to your questions about how to live a good life after newsletter promotion Another potential advantage: most researchers say that the effect will likely last for months or perhaps longer – similar to the pattern seen for many non-inverse vaccines. 'The immune system is incredible,' Hubbell says. 'It has a memory, and that memory lasts.' Currently, most treatments for autoimmune disease require more frequent treatment, often a regimen of daily medicine. In addition, inverse vaccines seem to have benefits beyond autoimmunity. They may work for allergies, which also involve an overreaction by the immune system – in this case to a food or environmental trigger rather than one's own body. In 2022, Miller and his colleague, University of Michigan biomedical engineer Lonnie Shea, published a small study with mice with peanut allergy. The animals who received an inverse vaccine were able to consume significantly more peanuts without symptoms than those who did not get the vaccine. Last month, Hubbell and several colleagues published a paper in Science Translational Medicine showing that their inverse vaccine could protect allergic mice from house dust mite antigens, a frequent cause of asthma, as well as antigens to chicken egg whites, a common experimental model for allergy. The protection held up through repeated exposures to the allergens over several months. And last year, Shea, the University of Michigan the biomedical engineer, published a paper looking at alpha-gal syndrome, a potentially severe allergy to meat caused by tick bites. Infected mice who were given an inverse vaccine showed significantly fewer symptoms than those who were given a placebo. 'We were able to basically convince the immune system that these proteins are not dangerous,' Shea says. At this point, it is difficult to say how long it will be before inverse vaccines are approved for human use. Miller, Shea, Hubbell, Santamaria and other researchers are involved in startup biotech companies working to develop them. Some larger pharmaceutical companies are also bullish on the approach, and are partnering with startups. In December, Genentech announced a partnership with Cour, the company started by Miller and Shea, that could be worth up to $900m. Last year, Parvus, the startup founded by Santamaria, entered into a collaboration with the pharmaceutical company AbbVie. Several inverse vaccines are now in the midst of or about to start phase two trials, small studies looking at how effective the treatment is in humans. Some scientists estimate that the first inverse vaccines could be available for use in three to five years. Others are less certain. 'I think it will take 10 years to have it nailed down,' Jabri says. 'But it could be shorter, or it could be longer.' Even so, nearly all are optimistic. 'Twenty years ago, I would have told you this wasn't possible, absolutely not,' says Miller. 'Today, I can say that it will happen. No doubt.'
