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Celiac.com 04/23/2015 - It's well-known that many people with celiac disease experience neuropathy and other nerve disorders. Now, a team of Israeli researchers are cautiously proposing a link between gluten reactions and ALS. The research team, from the Tel Aviv Medical Center, believes that the gluten sensitivity seen in people with celiac disease might have a connection with ALS, or amyotrophic lateral sclerosis. Their study linking tissue transglutaminase 6 antibodies to ALS is the first study to document a connection between ALS and antibodies to a particular enzyme. Also known as Lou Gehrig's disease, ALS is a progressive disease that attacks nerve cells and pathways in the brain and spinal cord, eventually causing paralysis. In the study, researcher Vivian Drory and her team found antibodies to an enzyme produced in the brain, called tissue transglutaminase 6 (TG6), in 23 out of 150 patients with ALS, but in only five of 115 healthy volunteer subjects. Furthermore, ALS patients showed higher concentrations of those antibodies. It's well documented that people with celiac disease produce antibodies to another transglutaminase, TG2, when they eat gluten, a protein in wheat, barley and rye. Interestingly, nearly half (45%) of patients with celiac disease also produce antibodies to TG6, even when they have no neurological symptoms. Droury's team set out to evaluate the prevalence of celiac disease-related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients. They conducted a case-control study in an ALS tertiary center, where they measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, along with IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex. Study subjects did not have any known autoimmune or gastroenterologic disorder, and none was receiving any immunomodulatory medications. The team found that ALS patients with antibodies to TG6 showed the classic picture of ALS and the typical rate of disease progression. The volunteers with antibodies to TG6 showed no signs of any disease. All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients. The team tested fifty patients and 20 controls for celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) tested seropositive for celiac disease-related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04). Average levels of IgA antibodies to TG6 were 29.3 (30.1) in patients and 21.0 (27.4) in controls (P = .02; normal, <26). Average levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10). In a subset of study participants, mean levels of deamidated gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in controls (normal, <16). None of the ALS patients or volunteers had the antibodies to TG2 that are commonly associated with celiac disease, but the ALS patients were more likely to show the genetic mutations that put them at risk for celiac disease. Drory said her team has begun to study TG6 antibody levels in patients newly diagnosed with ALS, and they will be testing the effects of a gluten-free diet in some of those that test positive. However, theirs is just one report, and Drory expects it will be at least a couple of years before the team has any solid results. Her team is also inviting further input from other centers, and study of their data. In the meantime, she warns ALS patients against adopting a gluten-free diet without "clear evidence of antibodies," because any imbalance of diet might prove harmful. It's also worth remembering that an association is not the same as a cause. At least one earlier study concluded that there was no association between TG6 antibodies and either neurological disease or gluten itself. The possibility of a link between celiac disease and a degenerative nerve disease like ALS is interesting, to say the least. The findings of this team will likely invite more examination of any connection between gluten reactions and nerve disorders, so stay tuned for any follow-up news. Source: JAMA Neurol. 2015 Apr 13. doi: 10.1001/jamaneurol.2015.48.
Celiac.com 01/30/2009 - Doctors from the Mayo clinic are proposing a new staging system for patients with Refractory Celiac Disease (RCD) after results of a recent study showed that their system offered greater accuracy and improved survival rates over the existing staging system. The new system will rely on the cumulative effect of 5 prognostic factors evaluated at the time of the refractory state diagnosis. Refractory Celiac Disease occurs when both the symptoms and intestinal damage continue or recur, regardless of strict adherence to a gluten-free diet. In Refractory Celiac Disease, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The goal of this study was describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD. The study was conducted by doctors Alberto Rubio–Tapia, Darlene G. Kelly, Brian D. Lahr, Ahmet Dogan, Tsung–Teh Wu, and Joseph A. Murray, all with the Mayo Clinic in Rochester, MN. The research teams assessed and compared clinical characteristics and outcomes in 57 patients with RCD: 42 with RCD I and 15 with RCD II. The team developed a scale that served as the basis for the new staging system. Using Cox regression, they assigned a point score to each of the various prognostic factors. They assigned a score of 0 to patients who showed no Refractory Celiac Disease factors. A score of 1 or 2 was assigned for presence of prognostic factors by rounding each score and taking the sum of all 5 factors for a total score. The team then applied the system to survival rates within the study: Stage I combined patients with a point score of 0 or 1 (n = 27), stage II patients with a point score of 2 or 3 (n = 16), and stage III patients with a point score of 4 (n = 14). Patients with total point scores of 0 (n = 15) or 1 (n = 12), showed overall 5-year survival rates of 93% and 100%, respectively. Patients with a score of 2 (n = 7) or 3 (n = 9) showed 5-year overall survival rates of 80% and 65%, respectively. Patients with a score of 4 (n = 10) or 5 (n = 4), the 5-year cumulative survival rates of 25% and 0%, respectively. For patients in stages I, II, and III, the 5-year cumulative survival rate was 96%, 71%, and 19%, respectively (P < .0001). Fifteen of the 57 patients died within 2 years of being diagnosed with RCD (8 with RCD I and 7 with RCD II). Over the five-year course of the follow-up, the overall survival was 70% for the entire cohort, 80% for RCD I, and 45% for RCD II. Most deaths were a result of refractory celiac disease, or to enteropathy-associated T-cell lymphoma (EATL). Refractory Celiac Disease generally carries a high rate of mortality, and the outcomes for RCD II have been especially poor because of the tendency for EATL to develop. Citing the results, the team is proposing a new staging system based on the cumulative effect of 5 prognostic factors investigated at the time of the refractory state diagnosis Gastroenterology 2009; 136:000–000
Celiac.com 07/24/2001 - In an effort to make food ingredient labels easier for everyone to understand, the Food and Drug Administration (FDA) is currently revising its food labeling laws. If Congress passes the current proposed legislation it will make life much easier for those with food allergies and intolerance. The Food Allergy Anaphylaxis Network (FAAN) spearheaded the yearlong label revision project and worked with 18 food companies to create voluntary guidelines for food labels that will help consumers avoid foods that could trigger an allergic reaction. The current recommended FAAN guidelines will identify the top eight allergens that cause 90 percent of food allergies, and will also avoid the use of technical food language in favor of easier to understand terms. For example, instead of using simply natural flavors on labels, the new labels would include the source of the ingredient: natural peanut or milk flavor. According to the guidelines common allergens such as peanuts, tree nuts like walnuts and pecans, fish, shellfish, eggs, milk, soy, and wheat should be clearly identified on all labels. On a positive note, the new FAAN guidelines have been voluntarily adopted by certain companies within the food industry for the benefit of the allergic consumer. Numerous consumer complaints and calls from the 6-7 million people in the USA with food allergies, not to mention the fear of lawsuits from the 150-200 people that die each year from them, were certainly motivating factors for them taking this important step. In any case, any change in food labeling practice would have to be an improvement over the present situation. The new FAAN guidelines, however, amount to only recommendations at this point, although Kelloggs and General Mills and several other companies have already adopted them. Legislation incorporating the FAAN guidelines has been proposed by representative Nita M. Lowey (D-NY) , which, if passed, would make them federal law in the USA. To encourage a stronger version of the proposed new labeling laws, contact your representatives now about this important issue!