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Celiac.com 12/13/2024 - The study investigates whether there is a causal relationship between autoimmune diseases and schizophrenia. Schizophrenia, a severe neuropsychiatric disorder, has been associated with immune system dysfunction in prior research. However, conflicting evidence has left the nature of this connection unclear. By using advanced genetic analysis, the researchers sought to determine whether autoimmune diseases and schizophrenia directly influence each other. Why Study Schizophrenia and Autoimmune Diseases? Schizophrenia is a complex disorder with genetic, environmental, and biological contributors. It affects approximately 1% of the global population and significantly reduces life expectancy. Autoimmune diseases, where the immune system mistakenly attacks the body, have also been linked to schizophrenia in observational studies. However, these links could be due to overlapping genetic or environmental factors rather than direct causation. Understanding these connections could pave the way for improved prevention and treatment strategies for both conditions. Study Design: Using Genetics to Uncover Causality This research used Mendelian randomization, a statistical method that analyzes genetic data to infer causality between factors. By examining genetic variations associated with both schizophrenia and 10 common autoimmune diseases, the study aimed to identify whether there are direct effects between the two. These diseases included conditions like celiac disease, lupus, type 1 diabetes, and psoriasis, among others. The bidirectional nature of the analysis meant that researchers looked at whether autoimmune diseases influenced schizophrenia and vice versa. A variety of statistical approaches were used to ensure robust results and account for confounding factors. Key Findings The study found distinct patterns in how schizophrenia and autoimmune diseases are linked: Autoimmune Diseases Increasing Schizophrenia Risk: Ankylosing Spondylitis: Genetic predisposition to this inflammatory arthritis was associated with a higher risk of developing schizophrenia. Autoimmune Diseases Decreasing Schizophrenia Risk: Celiac Disease, Type 1 Diabetes, and Lupus: Genetic markers for these conditions were linked to a lower risk of schizophrenia, challenging prior studies that suggested an increased risk. Schizophrenia Increasing Autoimmune Disease Risk: Schizophrenia was found to heighten the risk of certain autoimmune diseases, including inflammatory bowel disease (encompassing Crohn’s disease and ulcerative colitis) and psoriasis. No Causal Link Identified: Multiple sclerosis and rheumatoid arthritis showed no causal relationship with schizophrenia in either direction. Exploring Biological Mechanisms The study delved into why these links might exist. Several immune-related factors could explain the relationship: Immune Dysregulation: Schizophrenia and autoimmune diseases share immune system irregularities, such as imbalances in certain immune cells and altered cytokine levels. Genetic Overlap: Some genetic regions associated with schizophrenia also contribute to autoimmune diseases, suggesting shared pathways in their development. Inflammatory Triggers: Chronic inflammation and infections might simultaneously predispose individuals to both schizophrenia and autoimmune diseases. Antibodies and Neural Impact: In conditions like celiac disease, antibodies produced in response to gluten have been implicated in psychiatric symptoms, possibly linking immune responses to brain function. Study Strengths and Limitations This study was the first to use a large-scale genetic approach to comprehensively assess the relationship between schizophrenia and autoimmune diseases. By relying on genetic data, it avoided biases often present in observational studies. Sensitivity analyses further validated the results. However, the study had limitations: The genetic data came exclusively from individuals of European ancestry, so findings may not apply to other populations. It only included 10 autoimmune diseases, leaving the potential for overlooked associations with other conditions. Nonlinear relationships and environmental factors, such as stress or diet, were not accounted for. Implications for Those With Celiac Disease One of the most significant findings for individuals with celiac disease is the evidence suggesting a protective effect against schizophrenia. This aligns with earlier studies that found improvements in psychiatric symptoms for some schizophrenia patients who adopted a gluten-free diet. Although more research is needed, this connection underscores the potential importance of nutrition and immune health in managing mental health conditions. Why This Matters Understanding the links between autoimmune diseases and schizophrenia is crucial for advancing medical care. This research provides evidence of specific causal relationships, shedding light on potential shared biological mechanisms. For individuals with celiac disease, it offers reassurance that their condition may not increase—and could even reduce—their risk of schizophrenia. More broadly, the findings could inspire new treatment strategies that address the immune system to improve outcomes for those with schizophrenia. Read more at: bmcpsychiatry.biomedcentral.com Watch the video version of this article:

Celiac.com 02/03/2024 - Celiac disease is a complex condition influenced by a combination of genetic and environmental factors. Genetic testing, along with other diagnostic tools, helps in assessing the risk of celiac disease. Consultation with a healthcare professional is crucial for accurate diagnosis and management. Understanding celiac disease requires unraveling the complex genetic puzzle that underlies this autoimmune condition. Within the human genome, certain genes stand out as key players, influencing susceptibility and shaping the landscape of celiac disease. There are both common and uncommon genes that are related to celiac disease and gluten sensitivity, and here we will explore both. Common Genes Associated with Celiac Disease The number of genes associated with celiac disease is more than two, but there are two main genes that are commonly tested for celiac disease susceptibility. These genes are HLA-DQ2 and HLA-DQ8. HLA-DQ2: The majority of individuals with celiac disease (about 90-95%) carry the HLA-DQ2 gene. HLA-DQ8: Around 5-10% of individuals with celiac disease have the HLA-DQ8 gene. It's important to note that the presence of these genes doesn't guarantee the development of celiac disease. Additionally, the absence of HLA-DQ2 and HLA-DQ8 doesn't rule out the possibility of celiac disease, as there are cases of individuals with celiac disease who lack these genes, and there are less common genes that have been found to be related to the disease. Uncommon Genes Associated with Celiac Disease While HLA-DQ2 and HLA-DQ8 are the primary genes associated with celiac disease, other genetic factors may contribute to its development. Within the realm of celiac disease, the genetic narrative extends beyond the well-known HLA-DQ2 and HLA-DQ8 genes to the uncommon genes that contribute to the disease. While not as prevalent as their more recognized counterparts, several uncommon genes have also been found to be a factor in triggering celiac disease in some individuals. Non-HLA Genes Identified as Potential Risk Factors for Celiac Disease HLA-DQ2.5 Subtypes: Within the HLA-DQ2 category, specific subtypes such as HLA-DQ2.2 have been linked to celiac disease risk. HLA-DQ7: Although less common than HLA-DQ2 and HLA-DQ8, HLA-DQ7 has been identified as a potential risk factor. HLA-DQ4: While individuals with HLA-DQ4 are at lower risk compared to those with HLA-DQ2 or HLA-DQ8, this gene may still play a role in susceptibility. Other Non-HLA Genes: Genome-wide association studies (GWAS) have identified several non-HLA genes associated with celiac disease, including IL2 and IL21. Genes Related to Non-Celiac Gluten Sensitivity Intriguingly, the genetic landscape we traverse in celiac disease extends its influence beyond the boundaries of this autoimmune condition. Emerging research suggests a potential link between certain celiac-associated genes and non-celiac gluten sensitivity (NCGS). While NCGS lacks the autoimmune component seen in celiac disease, the overlap in genetic markers hints at shared mechanisms. Individuals with NCGS may also carry genetic variations that contribute to their sensitivity to gluten. Unraveling these connections broadens our understanding of gluten-related disorders and opens avenues for investigating the spectrum of gluten-related conditions. The intricate interplay of genetics in both celiac disease and non-celiac gluten sensitivity invites further exploration into the nuances of gluten-induced immune responses, paving the way for more comprehensive insights into gluten-related health issues. Summary In summary, while HLA-DQ2 and HLA-DQ8 are significant markers for celiac disease susceptibility, having these genes is not a definitive diagnosis, and not having them doesn't rule out the possibility of celiac disease. Other genetic and environmental factors contribute to the development of celiac disease. A diagnosis typically involves a combination of genetic testing, serological tests, and, in some cases, a biopsy of the small intestine. As we decipher the genetic blueprint, it becomes evident that celiac disease is not a one-size-fits-all scenario. The interplay of diverse genetic factors illuminates the variability in how the disease manifests and underscores the importance of individualized approaches to diagnosis and management. Additional Resources: NIH - Gene Reviews Celiac disease: From genetics to epigenetics Celiac Disease Genetics: Current Concepts and Practical Applications Journal of Medical Genetics - Genetics of Celiac Disease The genetics of celiac disease: A comprehensive review of clinical implications

Celiac.com 06/12/2023 - Celiac disease is an autoimmune disorder characterized by gastrointestinal symptoms and nutrient deficiencies. While genetic factors, particularly HLA association, play a significant role in its development, the exact environmental triggers remain unclear. Recent studies have proposed infections as potential contributing factors. With the Covid-19 pandemic causing a systemic inflammatory response and affecting the gastrointestinal tract, researchers in southern Sweden set out to investigate whether Covid-19 infection could increase the risk of developing celiac disease. The research team included Jesper Lexner, Ylva Lindroth and Klas Sjöberg. They are variously affiliated with the Department of Gastroenterology and Nutrition, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden; and the Division of Medical Microbiology, Department of Laboratory Medicine, Skåne University Hospital, Lund University, Lund, Sweden. The Covid-19 and Celiac Disease Connection To explore the potential association between Covid-19 infection and celiac disease, the researchers identified all patients, including children and adults, in the county of Skåne with newly diagnosed biopsy- or serology-verified celiac disease or positive tissue transglutaminase antibody tests (tTG-ab) from 2016 to 2021. They also identified individuals who tested positive for Covid-19 using PCR or antigen tests in 2020 and 2021. The Findings During the period from March 2020 to December 2021, there were 201,050 cases of Covid-19 in Skåne, and among them, 568 patients were diagnosed with celiac disease or had positive tTG-ab tests. Interestingly, only 35 of these patients had previously been infected with Covid-19. Contrary to initial expectations, the incidence of verified celiac disease and tTG-ab positivity was lower during the Covid-19 pandemic compared to before. The incidence rates of celiac disease were 21.1 and 22.4 cases per 100,000 person-years for patients with and without prior Covid-19 infection, respectively. Implications of the Study The findings of this study suggest that Covid-19 infection is not a significant risk factor for the development of celiac disease. While previous research has indicated that gastrointestinal infections may play a role in the pathogenesis of celiac disease, respiratory infections, such as those caused by the SARS-CoV-2 virus, appear to have less relevance in this regard. Study Limitations It is important to note that this study focused on a specific region in southern Sweden and the findings may not be generalizable to other populations or geographic areas. Further research involving larger and more diverse populations is warranted to validate these findings. Additionally, the study did not explore potential mechanisms underlying the connection between gastrointestinal infections and celiac disease pathogenesis, highlighting the need for future investigations in this area. Understanding the environmental triggers and risk factors associated with celiac disease is crucial for improving diagnosis, treatment, and prevention strategies. While the Covid-19 pandemic has posed significant challenges worldwide, this study suggests that Covid-19 infection does not increase the risk of developing celiac disease. Read more in BMC Gastroenterology volume 23, Article number: 174 (2023)

Celiac.com 05/27/2023 - Malignancy must be a concern for all of us with celiac disease. The association between increased mortality in celiac disease due to malignant disease has been known since 1962(1) . Subsequent studies have confirmed various types of malignancies occurring in celiac patients with the most frequent being lymphomas, which account for 51-72% of celiac disease-associated malignancy(2, 3) . Both small bowel lymphomas and adenocarcinoma, the most frequent celiac disease-associated malignancies, typically arise in the jejunum but also are found in the duodenum and ileum(2) . Other sites of carcinoma found in greater than expected numbers have been the mouth, pharnyx, lung, breast, and testes2, 3. Celiac disease-associated cancer is found in both child and adult celiacs(2). Enteropathy associated T-cell lymphoma (EATL) of the small bowel is the major lymphoma associated with celiac disease(2, 4). This type of non-Hodgkin lymphoma appears to be primarily associated with celiac disease and is known to increase in people with celiac disease who are 50-70 years of age(4) . There appears to be two forms of EATL, and one of them may originate during refractory celiac disease(2,4). Abnormalities in refractory celiac disease lymphocytes are similar to those of this form of EATL(3) . While the majority of patients with celiac disease have improved symptoms with a strict gluten-free diet, those with refractory celiac disease may be non-responsive because of complications due to the development of EATL(5). The Importance of a Gluten-Free Diet The exact rate of malignancy in celiac disease is unknown since much of the silent or asymptomatic form of the disease remains undiagnosed(5) . Also, the celiac disease status of patients with established lymphoma may never be determined, or may be missed at examination(2, 5). However, European studies have shown an increased mortality rate due to malignancies in celiac disease as high as two to nearly four times that of the non-celiac disease population(2) . Most deaths occurred in the first 3-4 years after diagnosis. Several studies have demonstrated the protective effect of a strict gluten-free diet against malignancy(2, 5) . There appears to be a clear correlation between increased cancer rates (comparing the celiac disease and non-celiac disease populations) and the amount of gluten ingestion. In one of the studies, the excess morbidity of patients on a strict gluten-free diet was only 1.2 compared to 10.7 in patients on a normal (gluten-containing) diet(5). After 5 years or more on a strict gluten-free diet, there appears to be no significant increase in the overall cancer risk compared to the non-celiac disease population. Furthermore, a strict gluten-free diet appears to specifically reduce EATL(6). The Importance of Early Diagnosis Conferring the protective effect of a gluten-free diet with early diagnosis is important in malignancies like lymphoma, which has a poor prognosis(5). The expected five-year survival of advanced small bowel lymphoma is 25-30%; that of intestinal T cell lymphoma is only about 25%7 . Furthermore, gastrointestinal lymphomas often are presented as high grade (i.e., more advanced) malignancy, and are often widespread(5,6). Unfortunately some cases of celiac disease are not diagnosed until presentation of lymphoma. T-cell lymphomas most often arouse the suspicion of undiagnosed celiac disease, but B-cell lymphomas exist in celiac disease as well(8). However, the diagnosis of lymphoma can be difficult to ascertain due to non-specific symptoms or symptoms similar to celiac disease(5,7). Presenting features of gastrointestinal lymphoma are similar to that of uncomplicated celiac disease; "Unexplained deterioration, abdominal pain, weight loss, severe muscle weakness, lymphadenopathy (disorder of the lymph nodes), abdominal mass and pyrexia (fever) should arouse suspicion of lymphoma."(5). Some patients may also have intestinal obstruction, perforation, or bleeding. Furthermore, patients with small bowel tumors (including adenocarcinoma) may present with abdominal pain, anemia, bleeding, weight loss, or obstruction(2, 7). Therefore, Ruskone-Fourmestraux and Rambaud suggest that "the diagnosis of coeliac disease must be made as early as possible and the diet commenced, even in asymptomatic subjects, after detailed and complete patient information."(6). Once diagnosed, therapy for lymphoma or adenocarcinoma may include surgery (such as resection of a portion of the intestine), chemotherapy, and/or radiotherapy(5). Regarding cancer, there is both good and bad news for those of us with celiac disease. While we have an increased risk of cancer, the risk is still very small for most celiacs. The symptoms of gastrointestinal cancers, and especially small bowel cancers, are similar to those of celiac disease itself. It appears, however, that with the exception of refractory celiac disease, a strict gluten-free diet over time may remove the increased chance of cancer due to celiac disease. Undeniably, our vigilant adherence and attitude toward the gluten-free lifestyle must be a mainstay and we must be up to the challenge. References: Gough KR, Read AE, Naish JM. 1962. Intestinal reticulosis as a complication of idiopathic steatorrhea. Gut 3: 232-39. Green PHR, and Jabri B. 2002. Celiac disease and other precursors to small-bowel malignancy. Gastroenterol Clin N Am 31:625-39. Seraphin P, and Mobarhan S. 2002. Mortality in patients with celiac disease. Nutrition Rev 60: 116-8. Catassi C, et al. 2002. Risk of non-Hodgkin lymphoma in celiac disease. JAMA 287:1413-9. Holmes GKT. 2002. Coeliac disease and malignancy. Digest Liver Dis 34:229-37. Ruskone-Fourmestraux A, and Rambaud JC. 2001. Gastrointestinal lymphoma: prevention and treatment of early lesions. Best Practice & Res Clin Gastroenterol 15:337-54. Gill SS, Heuman DM, and Mihas AA. 2001. Small intestinal neoplasm. J Clin Gastroenterol 33: 267-82. Freeman H, Lemoyne M, and Pare P. 2002. Coeliac disease. Best Pract & Res 16:37-49.

Celiac.com 12/26/2022 - Rates of celiac disease, and the use of medications that inhibit acid secretion, such as proton pump inhibitors, have both increased in recent decades. A team of researchers recently set out to explore potential connections between anti-secretory medication usage and risk for later development of celiac disease. Here's what they found. The research team included Benjamin Lebwohl, MD, MS, Stuart J. Spechler, MD, Timothy C. Wang, MD, Peter H.R. Green, MD, and Jonas F. Ludvigsson, MD, PhD. They are variously affiliated with the Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA; the Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden; the Division of Gastroenterology, Department of Internal Medicine, VA North Texas Healthcare System and UT Southwestern Medical Center, Dallas, Texas; and the Department of Pediatrics, Örebro University Hospital, Sweden. Population-based case control study In their population-based case control study, the team identified patients diagnosed with celiac disease across all of Sweden's pathology departments from July 2005 through February 2008. The team then matched patients by age and gender with up to five control subjects. The team identified previous prescriptions for proton pump inhibitors and histamine-2 receptor antagonists in all study subjects. The team then used conditional logistic regression to measure the connection between these prescriptions and a later diagnosis for celiac disease. Proton pump inhibitor prescriptions strongly associated with celiac disease The data show that people with previous proton pump inhibitor prescriptions had a strong association with celiac disease. Patients prescribed both proton pump inhibitors and histamine-2 receptor antagonists had a higher risk of celiac disease than those prescribed proton pump inhibitors alone or histamine-2 receptor antagonists alone. Conclusions From their findings, the team concludes that exposure to anti-secretory medications, such as proton pump inhibitors, is strongly correlated with a later diagnosis of celiac disease. This association remained, even after the team excluded prescriptions in the year preceding the celiac disease diagnosis, which points to the medications as a causal connection. The idea that certain medications can influence rates of celiac disease is not new. The idea that medicines like proton pump inhibitors can influence celiac disease rates is both new and potentially powerful information that could change the way we use those medicines, and the way we understand celiac disease development. Stay tuned for more on this and related stories. Read more in Dig Liver Dis. 2014 Jan; 46(1): 36–40. doi: 10.1016/j.dld.2013.08.128