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Celiac.com 10/02/2017 - For anyone following the efforts by ImmusanT to develop a vaccine for celiac disease, the company's recent presentations at the 2017 International Celiac Disease Symposium (ICDS) in New Delhi, India, were welcome news. Nexvax2® is a therapeutic vaccine intended to protect against the effects of gluten exposure while maintaining a gluten-free diet in HLA-DQ2.5+ patients with celiac disease. The company announced at ICDS 2017 that it has presented data showing the immunologic basis for the early clinical effects of gluten in celiac disease. Presented in two poster presentations and an oral presentation, the company says its data show that "early cytokine changes in blood following gluten ingestion could provide the basis for a new diagnostic for celiac disease in patients on a gluten free diet with an uncertain diagnosis," said Robert Anderson, MBChB, Ph.D., Chief Scientific Officer of ImmusanT. The company says its results are "significant" because celiac disease sufferers often adopt a gluten-free diet prior to being diagnosed by a doctor. This can cause problems and lead to unreliable or misleading results with current diagnostic tests. ImmusanT says that their data demonstrate that early changes in circulating cytokines after a single gluten exposure may offer a clinical way to assess celiac disease activity. The company says that the data, along with the potential to differentiate between celiac disease and non-celiac gluten sensitivity (NCGS) by assessing IL-2 levels, support the science behind targeted immunotherapies such as Nexvax2®. Read more at BusinessWire.com
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Celiac.com 04/14/2014 - Exposure to stressful stimuli, such as inflammation, cause cells to up-regulate heat shock proteins (Hsp), which are highly conserved immunomodulatory molecules. Research points to Hsp involvement in numerous autoimmune diseases, including autoimmune bullous diseases and celiac disease. To better understand the role of Hsp in autoimmune bullous diseases, a research team conducted the first investigation of the humoral autoimmune response to Hsp40, Hsp60, Hsp70, and Hsp90 in patients with dermatitis herpetiformis (DH; n = 26), bullous pemphigoid (BP; n = 23), and pemphigus vulgaris (PV; n = 16), the first representing a cutaneous manifestation of celiac disease. The research team included Kasperkiewicz M1, Tukaj S, Gembicki AJ, Silló P, Görög A, Zillikens D, Kárpáti S. They are affiliated with the Department of Dermatology at the University of Lübeck in Lübeck, Germany. In patients with active BP and PV, serum levels of autoantibodies against these Hsp matched the healthy control subjects (n = 9-14), while circulating autoantibodies against Hsp60, Hsp70, and Hsp90 increased at the active disease stage of DH. Further analysis showed that in patients who adopt a gluten-free diet, these anti-Hsp autoantibodies decreased in relation to serum autoantibodies against epidermal and tissue transglutaminase during remission of skin lesions. Larger groups of patients must be studied to confirm these findings, but these results indicate that autoantibodies against Hsp60, Hsp70, and Hsp90 play a key role in the development and maintenance of DH, possibly also in the underlying celiac disease, and may be important in potentially undiscovered disease biomarkers. Source: Cell Stress Chaperones. 2014 Mar 19.
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Celiac.com 12/26/2010 - Should everyone with symptoms of celiac disease go on a gluten-free diet? Current practice allows many patients with symptoms of celiac disease, but no gut damage, and thus no official diagnosis, to forgo a gluten-free diet. In a new study, researchers found that people with celiac disease symptoms have the same distinctive metabolic fingerprint as patients with full-blown disease, and who must follow a gluten-free diet to avoid permanent damage to the gut. The new study, by Ivano Bertini and colleagues, is stirring up the discussion about just which patients with symptoms of celiac disease should follow a gluten-free diet. Their research shows that people currently diagnosed as "potential" celiac disease patients and not advised to follow a gluten-free diet may not be "potential" patients at all. Celiac disease is widely regarded as undiagnosed or misdiagnosed. For their study, the researchers used magnetic resonance metabolic profiling to analyze the biochemical markers in the blood and urine of 61 patients with celiac disease, 29 with potential celiac disease, and 51 healthy people. The researchers found that people with unproven celiac disease largely shared the same profile as those with confirmed celiac disease and that the biochemical markers in both groups differed sharply from those of healthy individuals. The researchers conclude that their findings "demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of gluten-free diet in patients with potential celiac disease, as recently suggested by prospective clinical studies." The authors do note receiving funding from Boehringer Ingelheim Italy. Source: American Chemical Society Journal of Proteome Research
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GWAS Meta-Analysis Supports Existence of Autoimmune Clusters
Jefferson Adams posted an article in Latest Research
Celiac.com 01/27/2010 - New research indicates that the same genetic variants that make a person more susceptible for developing one set of autoimmune diseases may actually make them less susceptible to others. A Stanford University research team collaborated with a California hospital and clinical center to perform meta-analysis of genome-wide association studies on half a dozen autoimmune conditions, including type 1 diabetes and rheumatoid arthritis. The team uncovered a pattern in the grouping of specific diseases based on SNP data, with certain variables that increased risk for developing some conditions while protecting against others. SNPs are short for "single nucleotide polymorphisms — pronounced "snips." They are DNA sequence variations that occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered The SNP data led the team to suggest that there may be benefits in classifying autoimmune diseases according to shared genetic factors rather than considering them a single group. "Maybe we should stop considering all autoimmune diseases in one lumped category," senior author Atul Butte, a pediatric and bioinformatics researcher at Stanford University and director of the Lucile Packard Children's Hospital's Center for Pediatric Bioinformatics, says in a statement. "It looks as if there may be at least two different kinds." The team points out that all autoimmune diseases share common disease mechanisms, but that certain autoimmune diseases share more such mechanisms than do others. Past research suggests that individuals with type 1 diabetes face greater risk of developing autoimmune diseases such as autoimmune thyroid disease, multiple sclerosis, and celiac disease. And, they added, at least one SNP has been discovered to have opposing effects under varying autoimmune conditions: the G allele of that SNP, called rs2076530, is more common in individuals with type 1 diabetes or rheumatoid arthritis whereas those with systematic lupus erythematosus typically show the A allele. Given the strong connection between celiac disease, diabetes and other auto-immune conditions, the data seem intriguing. These discoveries led Butte and his colleagues to speculate about the way in which genetic factors relate to autoimmune disease clusters. The team used meta-analysis to assess 573 SNPs in several GWAS of six autoimmune diseases — type 1 diabetes, rheumatoid arthritis, Crohn's disease, multiple sclerosis, autoimmune thyroid disease, and ankylosing spondylitis — and five non-autoimmune diseases. By looking closely at alleles associated with each disease and determining the strength of these associations, the team crafted a so-called "genetic variation score" to evaluate connections between certain alleles and diseases across multiple genotyping platforms. The team evaluated nearly 600 SNPs. They found nine SNPs in which one allele appears to raise individual risk for multiple sclerosis and autoimmune thyroid disease, while lowering the risk for rheumatoid arthritis and ankylosing spondylitis. The alternative alleles for these SNPs, meanwhile, showed the opposite effect. "What was surprising was our finding that at nine locations generally associated with autoimmunity risk, where a particular chemical unit conferred a heightened risk of certain autoimmune diseases, but reduced risk of getting certain others," noted lead author Marina Sirota, who serves in a graduate capacity in Butte's Stanford University lab. Based on their findings, the research team proposes at least two distinct groups of autoimmune diseases: one containing rheumatoid arthritis and ankylosing spondylitis and another containing multiple sclerosis and autoimmune thyroid disease. In the mean time, the team observed, type 1 diabetes appeared to have similarities with both of groups; having some characteristics of autoimmune thyroid disease, but not of multiple sclerosis. Crohn's disease, in contrast, showed no such cluster with either group. The results will likely help pave the way for a more complete understanding of the biological pathways at play in these autoimmune diseases. They may also give researchers a better sense of how to apply existing therapies, and even how to create new ones. "Several of these nine interesting SNPs we've found are located in or near genes that code for molecules found on cell surfaces," Butte said, "which makes them potentially easier targets for the drugs pharmaceutical researchers are best at producing." The team expects the number and nature of SNPs involved will likely grow as more autoimmune disease GWAS reveal new genetic variants associated with these and other diseases. "As more genomic information becomes available on increasingly advanced platforms, this sort of analysis can be done on more diseases, possibly hundreds of them," Sirota noted. Source: GenomeWeb News- 1 comment
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Celiac.com 03/26/2009 - The recent discovery that people with celiac disease harbor antibodies that are specific for deamidated gliadin peptides (DGP), which are the product of tTG binding to gliadin peptides, offers a chance to examine the connection between the production of anti-tTG IgA and the antibodies against DGP in celiac patients. A group of researchers led by Doctors Marietta, Rashtak, and Murray from the Mayo Clinic in Rochester, MN recently set out to make just such an examination, and a report on their study appears in the February issue of the World Journal of Gastroenterology. Their data show that the blood level of anti-tTG IgA shares a significant connection with the blood level of anti-DGP of both the IgG and IgA isotypes in people with untreated celiac disease. The same data showed only a weak connection between the production of anti-tTG IgG and anti-DGP IgG/IgA. Moreover, the results show that the immune response by T and B cells to deamidated gliadin differs at the most basic level from the immune response by T and B cells to tissue transglutaminase in celiac patients. Their results also indicate, however, that the immune responses against deamidated gliadin and tTG are substantially connected, and thereby offer support for the hapten-carrier theory for the origin of anti-tTG IgA. World Journal of Gastroenterology; February, 2009.
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FDA Supports Food Allergen Labeling Bill
Scott Adams posted an article in Product Labeling Regulations
Celiac.com 12/19/2003 - In a press release dated November 24, 2003, FDA Commissioner, Mark B. McClellan, M.D., Ph.D., applauded the Senate Health, Education, Labor and Pensions Committee reporting out several health-related bills. Among the bills unanimously approved by the Committee was S. 741, a bill that includes the proposed Food Allergen Labeling and Consumer Protection Act of 2003. Action by the Committee took place on November 21. I wish to thank the Committee Chairman Senator Judd Gregg, Ranking Member Senator Edward Kennedy and the rest of the Committee members for taking these actions, Dr. McClellan said, and I look forward to continuing to work with the members of both houses of Congress toward the enactment of these bills. The Food Allergen Labeling and Consumer Protection Act will provide improved food labeling to better inform consumers who suffer from food allergies. Having the endorsement of the FDA will be key as we look ahead to floor action by the full Senate in early 2004. Andrea Levario Co-Chair, American Celiac Task Force
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