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Celiac.com 10/23/2024 - Cardiovascular diseases, such as coronary artery disease and stroke, have long been connected with various immune-mediated disorders due to the role inflammation plays in both conditions. This study explores whether there is a genetic connection between cardiovascular diseases and specific immune-mediated diseases, with a particular focus on psoriasis. Psoriasis is a chronic inflammatory condition that has previously been associated with an increased risk of cardiovascular disease. However, it is unclear whether the genetic risk factors for cardiovascular disease are also linked to an increased risk of psoriasis and other immune-related conditions. Study Objectives The main goal of the study was to investigate whether genetic predispositions to coronary artery disease and stroke also increase the risk of developing psoriasis or other immune-mediated diseases. The researchers utilized a method called Mendelian randomization, which uses genetic data to determine whether there is a causal relationship between two traits, as opposed to just an observed association. By using large datasets from genome-wide association studies, the study aimed to uncover whether genetic predictors of cardiovascular disease are directly linked to immune-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Methods and Data To conduct the analysis, the study used Mendelian randomization to evaluate the genetic links between cardiovascular disease and immune-mediated diseases. This approach is particularly effective in differentiating causality from correlation because it uses genetic markers as proxies for risk factors. The researchers analyzed summary data from genome-wide association studies for coronary artery disease, stroke, psoriasis, and nine other immune-mediated diseases. The data included a large sample of participants, with over 1.1 million individuals for cardiovascular disease traits and nearly 500,000 for psoriasis. The study specifically examined whether genetic markers associated with coronary artery disease and stroke were linked to an increased risk of developing psoriasis or any of the other immune-mediated diseases. Key Findings The results of the study revealed that genetic predictors for both coronary artery disease and stroke were significantly associated with an increased risk of psoriasis. In particular, genetic risk factors for coronary artery disease were found to increase the risk of developing psoriasis by about 7%, while genetic risk factors for stroke increased the risk by 22%. Interestingly, when adjustments were made for stroke risk, the association between coronary artery disease and psoriasis became statistically insignificant. This suggests that there may be a shared genetic component that links both cardiovascular diseases and psoriasis, rather than two separate pathways. On the other hand, the study found no significant genetic link between cardiovascular disease risk factors and other immune-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease. This finding was somewhat unexpected, as these diseases also involve inflammation, which is thought to be a common factor in both cardiovascular disease and immune-mediated disorders. Genetic Risk and Celiac Disease The study also explored the relationship between genetic predictors of cardiovascular disease and various immune-mediated diseases, including celiac disease. Data from 4,533 cases of celiac disease and 10,750 controls were included in the analysis. The results indicated no significant association between genetic risk factors for cardiovascular disease—such as coronary artery disease or stroke—and the risk of developing celiac disease. This finding suggests that while cardiovascular genetic factors may influence the risk of developing psoriasis, they do not appear to have the same effect on celiac disease or other immune-mediated conditions. Understanding the Relationship Between Psoriasis and Cardiovascular Disease The discovery that genetic risk factors for cardiovascular disease are linked specifically to psoriasis, but not to other immune-mediated diseases, points to the possibility of a unique shared biological mechanism. Psoriasis is a disease driven by inflammation, and inflammation is also a key factor in the development of cardiovascular diseases like coronary artery disease and stroke. However, the study’s findings suggest that this connection may not extend to all immune-mediated diseases, challenging previous assumptions about the broad relationship between cardiovascular disease and inflammation-driven conditions. One possible explanation for this connection could lie in the specific inflammatory pathways involved in both cardiovascular disease and psoriasis. Psoriasis is known to involve certain inflammatory cellular and cytokine pathways, and these same pathways may play a role in the development of cardiovascular disease. However, these pathways may not be as significant in other immune-mediated diseases, which could explain the lack of genetic association with conditions like rheumatoid arthritis and inflammatory bowel disease. Implications for Treatment and Future Research The findings of this study have several important implications. First, they highlight the need for further research into the shared genetic mechanisms underlying cardiovascular disease and psoriasis. Understanding these mechanisms could lead to the development of new treatments that target both conditions. For example, therapies that reduce inflammation in psoriasis patients could potentially help lower their risk of cardiovascular disease, and vice versa. Second, the study underscores the importance of personalized medicine. As more is learned about the genetic links between different diseases, it becomes increasingly possible to develop tailored treatments that address an individual's unique genetic risk factors. For patients with psoriasis who are also at risk for cardiovascular disease, this could mean more targeted interventions that address both conditions simultaneously. Implications for Those with Celiac Disease The study’s findings highlight the importance of understanding the genetic overlap between cardiovascular disease and psoriasis, but they also underline the distinction when it comes to celiac disease. For those with celiac disease, the results are reassuring as they show no genetic link between cardiovascular risks and the condition. This separation emphasizes that while shared inflammatory pathways may exist between certain immune-mediated diseases and cardiovascular disease, celiac disease does not appear to be influenced by these cardiovascular genetic factors. As such, this research may provide a better understanding of how different immune-mediated diseases interact with cardiovascular health, guiding future research and treatment strategies. Read more at: jamanetwork.com

Celiac.com 02/08/2023 - Arthritis is a common problem for many people with celiac disease. And patients with celiac disease get rheumatoid arthritis twice as much as non-celiacs. However, the connection between arthritis and celiac disease is not well understood. A number of studies have found connections between celiac disease and arthritis. The connections are still not well understood, but here are some of the main findings. Celiac Disease and Juvenile Idiopathic Arthritis A recent study shows that JIA is nearly three times more common among children with celiac disease than in the general population. Other studies support this finding. We also know that celiac disease can occur in JIA patients with no celiac symptoms. Celiac Disease and Rheumatoid Arthritis In adults with celiac disease, rheumatoid arthritis strikes nearly 9 per 10,000 person-years and about 5 per 10,000 person-years in matched factors over a follow-up of about nine years. Rheumatoid arthritis occurs nearly twice as often among adults with celiac disease. It's important for individuals with celiac disease to be aware of the possibility of developing rheumatoid arthritis and to inform their doctor if they have any joint symptoms. High rates of Celiac Disease Antibodies in Adult Rheumatology Patients We know that studies have shown high rates of celiac antibodies in adult rheumatology patients. A recent study showed celiac antibodies in 3% of adult rheumatology patients, which provides support for celiac screening in people with rheumatological issues might be good practice. Because of the extra risk, it is important for clinicians to watch closely for signs of arthritis in celiac patients with joint symptoms, as early arthritis detection and treatment leads to much better outcomes. Look for researchers to learn more about the connections between arthritis and celiac disease going forward. Stay tuned for more on this and other important stories about celiac disease. Read more on celiac disease and arthritis Could an Old Arthritis Drug Treat Celiac Disease and Allow Celiacs to Eat Gluten Again? Celiac Disease More Common in Patients With Juvenile Idiopathic Arthritis Celiac Disease Possible in Juvenile Idiopathic Arthritis Patients with no Celiac Symptoms

Celiac.com 12/23/2022 - Compared with the general population, children with celiac disease are nearly three times as likely to develop juvenile idiopathic arthritis, while adults with celiac disease are nearly twice as likely to be diagnosed with rheumatoid arthritis. Celiac disease is tied to numerous immune-mediated conditions, but, so far, researchers haven't nailed down any solid epidemiological connection between celiac disease and juvenile idiopathic arthritis or rheumatoid arthritis. A new study changes that. Here's how. Population-based Cohort Study Using a population-based cohort, a team of researchers recently set out to determine the risk of juvenile idiopathic arthritis and rheumatoid arthritis in people with celiac disease. The research team included John B. Doyle, MD; Benjamin Lebwohl, MD, MS; Johan Askling, PhD; Anders Forss, MD; Peter H.R. Green MD; Bjorn Roelstraete, PhD; Jonas Söderling, PhD; Jans F. Ludvigsson, and Jonas MD, PhD. They are variously affiliated with the Celiac Disease Center, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA; the Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; the Department of Pediatrics, Orebro University Hospital, Orebro, Sweden. Celiac Disease Data Used to Spot Patients Using a national histopathology database in Sweden, the team identified patients diagnosed with biopsy-proven celiac disease between 2004 and 2017. They then matched each patient by age, sex, calendar year, and geographic region against people from the general population. They then used Cox proportional hazards models to calculate the incidence and estimated the relative risk of juvenile idiopathic arthritis in celiacs aged eighteen and under, and of rheumatoid arthritis in people with celiac disease aged eighteen and over. The team found just over 24,000 celiacs, whom they then matched to more than 117,000 people from the general population. Juvenile Idiopathic Arthritis Rates Triple for Celiac Youth & Rheumatoid Arthritis Rates Double for Adults Among people under 18 years old, the incidence rate of juvenile idiopathic arthritis was 5.9 per 10,000 person-years in patients with celiac disease and 2.2 per 10,000 person-years in the general population over a seven year follow-up. Among individuals 18 or over, the incidence of rheumatoid arthritis was 8.4 per 10,000 person-years in celiac disease and 5.1 per 10,000 person-years in matched comparators over a follow-up of 8.8 years. KIA is nearly three times more common among children with celiac disease than in the general population, while rheumatoid arthritis occurs nearly twice as often among adults with celiac disease. Based on their findings, the team advises clinicians caring for celiac patients with joint symptoms to be vigilant for signs of juvenile idiopathic arthritis or rheumatoid arthritis in those patients. Read more in the American Journal of Gastroenterology

Celiac.com 09/24/2019 - Currently, physicians do not routinely conduct celiac disease screening in patients with rheumatological diseases, as these people are not considered to have high risk for celiac disease. A team of researchers recently set out to determine rates of celiac disease serological markers in a group of patients with rheumatological issues. The research team included Giacomo Caio, Roberto De Giorgio, Francesco Ursini, Silvia Fanaro, and Umberto Volta. They are variously affiliated with the Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; the Mucosal Immunology and Biology Research Center, Massachusetts General Hospital – Harvard Medical School, Boston, Massachusetts, USA; the Department of Medical Sciences, University of Ferrara, Ferrara, Italy; the Department of Health Sciences, University of Catanzaro “Magna Graecia”; and the Centre of Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London. The team screened blood from 230 rheumatological patients for celiac disease by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 total patients, the team found 67 patients with rheumatoid arthritis (RA), 52 with Sjögren’s syndrome (SjS), 42 with systemic sclerosis (SCL), 35 with systemic lupus erythematosus (SLE), 15 with mixed connective tissue disease, 11 with polymyositis and 10 with dermatomyositis. The results showed TTG IgA antibodies in a total of 7 out of 230 cases, or 3%. They also showed such antibodies in 3 of 42 SJS cases, 2 of 42 SCL cases, 1 of 67 RA cases, and 1 of 35 SLE sera. All seven samples were also positive for DGP IgG and EMA IgA. DGP IgG antibodies were the most common, showing up in 16 total samples. High rates of celiac disease antibodies in adult rheumatology patients suggest that celiac disease screening might be a good idea for people with rheumatological issues. Read more at Gastroenterology Hepatology Bed Bench. 2018 Summer; 11(3): 244–249.

Celiac.com 06/20/2019 (originally published 07/12/2010) - Autoimmune diseases taken together are the third leading cause of death in the US. The list of autoimmune diseases is long and varied—M.S., type 1 diabetes, lupus, Hashimoto’s thyroiditis, rheumatoid arthritis, Sjogren’s, and fibromyalgia to name just a few. But the autoimmune disease celiac, unlike all the others, has a unique feature—it’s the only autoimmune disease where the exact trigger is known. Gluten is the trigger for celiac disease and when that trigger is removed the body stops destroying its own small intestine. Why is this profound? Two reasons: There is no other autoimmune disease where the exact trigger is known. Gluten and the damage it causes to the small intestine may very well be the root cause of other autoimmune diseases! We have appreciated the interesting phenomenon where people “develop” gluten intolerance at different ages. It used to be perplexing because it was assumed that if the problem was genetically driven, as soon as the body received its first gluten “insult” damage should begin to occur. When patients stated that they felt perfectly fine until a certain age, it was thought that the damage had probably begun far earlier but the patient had just not noticed. What we have come to realize is that a genetic propensity plus the presence of gluten in the diet are only two of the three necessary constituents of the puzzle—the third is damage to the small intestine. A completely healthy, intact small intestine seems to be quite able to defend itself against gluten. But once damage has occurred, the gut becomes “leaky” and not only can digestive complaints result but symptoms arise in other body systems. There has been proof for many years that the intestine is not the only tissue targeted by the immune reaction to gluten. The prime example of this is a disease called dermatitis herpetiformis where the gluten sensitivity manifests primarily in skin, with only mild or no intestinal involvement. Now, more recent research reveals that perhaps a vast number of autoimmune diseases may also involve an immune response to dietary gluten as well as its consequent autoimmune reaction to tissue transglutaminase. This may be the main immunologic cause. [Note: Although we typically think of tissue transglutaminase as an enzyme in the gut, it is, in fact, an enzyme found throughout the body. This is perhaps another reason why gluten has such far-reaching effects in other systems of the body.] The substance that dictates the permeability between the barrier cells that line the small intestine is called zonulin. Increased zonulin causes the intestine to become leaky, thereby allowing substances to leave the intestine that normally shouldn’t. Research has shown that in patients with celiac disease, gliadin activates zonulin signaling, leading to increased intestinal permeability. But how does this extend to other autoimmune diseases? Dr. Alessio Fasano performed a brilliant study on rats that were genetically predisposed to develop type 1 diabetes. The premise was that if the gut was not affected negatively by zonulin and remained intact and healthy, then perhaps the auto-antibodies made against specific cells of the pancreas that create diabetes would be prevented from leaving the gut and thereby stopped from causing damage to the pancreas. Sure enough 2/3 of these rats who were highly predisposed to develop diabetes did not! This study was the first time that an autoimmune disease was prevented by blocking intestinal permeability. It further puts a new face on the entire concept of how and why autoimmune disease develops. We’ve always thought that the genetic predisposition was an overriding characteristic of autoimmune diseases that overshadowed any effort to sublimate it. This study opens a new field of investigation into the relationship between the health of the intestine and the basis of many diseases. Imagine if the “unknown trigger” of autoimmune disease turns out to be gluten and its effect of creating a leaky gut! It is for this reason that I am so passionate about early diagnosis of gluten intolerance. Whether it be celiac disease or gluten sensitivity, the effect that gluten imposes on the integrity of the small intestine has far-reaching implications. I see it clinically in my patients on a daily basis, but the above research puts a point on it that we must consider seriously. A study from Italy showed that the longer gluten sensitive people eat gluten, the more likely they are to develop autoimmune diseases. They found that in childhood celiacs, the prevalence of autoimmune disease rose from a baseline of 5% at age 2 to almost 35% by age 20. Imagine if screening of all children for gluten intolerance resulted in reductions of future autoimmune diseases! I am currently working on a program with my patients who are gluten intolerant to restore their small intestines to the healthiest possible condition. This is important from the obvious viewpoint that optimal digestion and absorption is critical to good health. But it is also vital from the perspective of understanding and managing zonulin and its long-term effects on health. I would recommend that you take the following steps to ensure that you are doing everything you can to restore your small intestine to optimal functioning. Have a comprehensive stool analysis performed to ensure that no pathogenic organisms (bacteria, amoeba, parasites, etc) are present. Such a test should also measure the effect of your body’s enzymes to see how effectively your food is being broken down and absorbed. It should also assess the health of your intestinal bacteria or probiotics. Eliminate dairy foods from your diet. There is considerable evidence to suggest that consuming milk from other mammals is not conducive to good health, especially in our digestive tracts. The inflammation that dairy can cause could well be contributing to a leaky gut, despite the elimination of gluten. Once you have taken the above steps, see how you’re feeling. Some patients require supplements such as glutamine, quercitin, reduced glutathione, N-acetylcysteine, omega 3 fatty acids, and vitamins A, E, B and zinc to help the intestinal lining heal fully. Once the above have been done, have a lab test performed for leaky gut. It’s called a lactulose/mannitol test and will show whether large molecules are crossing the intestinal barrier. This is a non-invasive, non-drug test. Just to reiterate: encourage parents you know to have their children evaluated for gluten intolerance. The more we can affect an early diagnosis, the healthier our future generations will be. Last but not least, show your doctor this data. There is still too much ignorance in our profession about gluten and its broad reaching negative effects. I hope you find this information helpful. Many of the steps mentioned above are best administered with the help of a clinician so let me know if I can assist you to find someone in your area who can help. References: Scandinavian Journal of Gastroenterology. 2006 Apr;41(4):408-19. Annals N Y Academy Science. 2009 May;1165:195-205. “Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms.” Clinical Gastroenterology & Hepatology. 2005 Apr;3(4):335-41. “Permeability, zonulin production, and enteropathy in dermatitis herpetiformis.” Gut. 2003 Feb;52(2):218-23. “Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.”