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Celiac.com 09/02/2008 - Thanks to a team of researchers based in Great Britain, doctors may soon have a powerful new diagnostic tool to help them in their efforts to combat the damage caused by celiac disease. Their new discovery concerns people with celiac disease who may also develop neurological disorders. The research team was made up of Marios Hadjivassiliou, MD, Pascale Aeschlimann, BSc, Alexander Strigun, MSc, David Sanders, MD, Nicola Woodroofe, PhD, and Daniel Aeschlimann, PhD. The team recently investigated the nature of gluten sensitivity by isolating a unique neuronal transglutaminase enzyme and examining whether it is the focus of the immune response in celiac patients with neurological dysfunction. About one in ten people with celiac disease also suffer from associated neurological disorders, mainly from a condition involving the cerebellum called gluten ataxia, and another involving the peripheral nerves called gluten neuropathy. For many people celiacs with gluten ataxia, their neurological problems are their sole symptom. Only about 1 out of 3 people with gluten ataxia and celiac disease will show classic intestinal damage when given a biopsy. This can make proper diagnosis difficult for them. Also, there’s presently no reliable way to predict which people with gluten intolerance might develop neurological problems. Most people familiar with celiac disease know that gastrointestinal discomfort is one of the most common symptoms. The antibody most commonly associated with such discomfort is called anti-transglutaminase 2 IgA. This is one of the main antibodies that doctors commonly look for when evaluating possible cases of celiac disease. Anti-TG2 antibodies are pretty much exclusive to people with celiac disease, and are associated with both untreated clinically symptomatic celiac disease, and with the latent form of the disease. This makes the presence of anti-TG2 antibodies an excellent diagnostic indicator of celiac disease. Anti-TG2, however, may not be the best indicator in every case of celiac disease. One example is in cases of dermatitis herpetiformis, which is an external skin reaction to gluten. Most people with dermatitis herpetiformis have a persistent itchy skin rash, and while the majority of cases show intestinal damage with a biopsy, patients rarely experience intestinal discomfort associated with classic celiac disease.1 There is also reliable data that point to a role that anti-TG3 plays in cases of dermatitis herpetiformis.2 This indicates that the nature of a given individual’s immune response may determine how celiac disease manifests itself within that individual. That hypothesis seems to be born out by the research team’s discovery that another antibody, called anti-transglutaminase 6 IgG and IgA response is widespread in gluten ataxia, completely outside of any intestinal symptoms. These antibodies are not found in healthy control patients or in patients with neurological conditions that had clear genetic causes. Both groups showed no anti-TG6 in their blood samples. The research team took blood samples from 20 patients with newly diagnosed celiac disease before the patients began a gluten-free diet. The team confirmed the presence of celiac disease with duodenal biopsy and made sure the patients had no patients had no evidence of neurological problems. The team then took blood samples from 34 patients with Gluten Ataxia, which they defined as otherwise sporadic idiopathic ataxia with positive IgG and/or IgA anti-gliadin antibodies. The also took samples from another17 patients with peripheral idiopathic neuropathy (PN) who tested positive for anti-gliadin antibodies. These 17 patients tested negative for anti-MAG and anti-GM1 and had no evidence of intestinal damage on biopsy. The team used three separate control groups. The first was a group with genetic ataxia, which included 18 patients with ataxia that was genetic in nature, or with a clear family history of autosomal dominant ataxia. The second control group of 14 patients included cases of diseases that were immune-mediated, but not tied to gluten-sensitivity (such as vasculitis, viral cerebellitis, paraneoplastic ataxia, GAD ataxia). Lastly, the team used blood samples from 19 healthy individuals as another control group. The research team used recombinant human transglutaminases to develop ELISA and inhibition assays with which they measured blood samples of patients with gluten sensitive gastrointestinal and neurological disorders, along with several control groups that included unrelated inherited or immune conditions, for the presence and specificity of autoantibodies. The team found that the blood samples of patients with celiac disease and gluten ataxia contain IgA and IgG class antibodies to TG6 that are not present in the healthy control patients or in patients with neurological conditions that had clear genetic causes. At present, doctors test for celiac disease by checking the HLA type, and looking for the presence of anti-gliadin and anti-transglutaminase 2 antibodies. The results of this study indicate that the presence of anti-transglutaminase 6 can help to pinpoint patients with gluten sensitivity that may be at risk of developing neurological disease. Forthcoming: Annals of Neurology Footnotes: 1. Marks J, Shuster S, Watson AJ. Small bowel changes in dermatitis herpetiformis. Lancet 1966; 2:1280-1282. 2. Sárdy M, Kárpáti S, Merkl B, Paulsson M, and Smyth N. Epidermal transglutaminase (TGase3) is the autoantigen of Dermatitis Herpetiformis. J Exp Med 2002; 195:747-757.

Celiac.com 11/21/2008 - Not much is known about what effects, if any, a gluten-free diet might have upon gastroesophageal reflux disease-related symptoms (GERD-rs) in people with celiac disease. A team of researchers recently set out to assess the recurrence of GERD-rs, in celiac patients with nonerosive reflux disease (NERD). Out of a total of 105 adult patients with celiac disease, the team found 29 with celiac disease who presented with the NERD. Those 29 were enrolled in the study, and compared against a control group of thirty non-celiac patients with NERD. After 8 weeks of PPI treatment the team found that 25 (86.2%) celiac patients saw GERD-rs resolve, compared to just 20 (66.7%) control subjects. The team used clinical means to assess recurrence of GERD-rs at 6, 12, 18, and 24-month intervals after initial proton-pump inhibitor (PPI) treatment were withdrawn for 8 weeks. In the celiac disease group, just five patients (20%) had a recurrence of GERD-rs at 6 months, but none had recurrence at 12, 18, and 24 months, while the control group showed recurrence in six of 20 controls (30%) at 6 months, in another six (12/20, 60%) at 12 months, in another three (15/20, 75%) at 18 months, and in another two (17/20, 85%) at 24 months. This is the first study to evaluate the effect of a gluten free diet in the nonerosive form of GERD in patients with celiac disease, via a clinical long-term follow-up, and the results suggest that a gluten free diet could be helpful reducing GERD symptoms and in preventing of their recurrence. J Gastroenterol Hepatol. 2008;23(9):1368-1372.

Celiac.com 05/06/2008 - In the majority of people with celiac disease,strict adherence to a gluten-free diet can result in a quality of lifethat is on par with non-celiacs. Still a small percentage of celiacsseem to suffer from persistent gastrological discomfort in the form ofirritable bowel or irritable-bowel-like symptoms. Very few studies havebeen done on persistent gastrological problems in adults with celiacdisease. Those that have been done rely upon univariate statisticalanalysis in clinical samples at the secondary or tertiary care leveland fail to assess the potential influence of non-celiac diseasespecific factors, which are considered to be a risk factor of irritablebowel syndrome (IBS), such as mental disorders, or gender. Ateam of researchers made up of doctors Winfried Hauser, Frauke Musial,Wolfgang Caspary, Jurgen Stein, and Andreas Stallmach set out todetermine rates of irritable bowel syndrome, irritable bowelsyndrome-related symptoms, and consecutive health care-seeking behaviorand their influence upon health-related quality of life (HRQL) and anyconceivable bio-psychosocial factors influencing adult patients withceliac disease. The research team made a medical and socio-demographicsurvey of 1000 adult celiac patients from the German Celiac Society bypost. The medical portion of the survey included bowel history. Theteam also had patients fill out a Short Form Health Survey (SFHS),along with the Hospital Anxiety and Depression Scale. 516 ofthe questionnaires came back completed. Respondents were similar ingender ratio and median age from the whole membership directory of theGerman Celiac Society, a group of more than 18,000 people who reportedsuffering from celiac disease at the age of 18. Of these, 213 (41.3%)had a diagnosis of celiac disease that was made by a duodenal biopsy,37 (7.2%) by serological tests (celiac disease-specific antibodies), 34(6.6%) using stool tests for trans-glutaminase antibodies, and 232(45.0%) using intestinal biopsy and serological tests. A totalof 446 patients indicated that they had biopsy-proven celiac disease. Of these 446patients, 18 were excluded because they indicated adherence to agluten-free diet for less than 1 year. Sixteen patients were tossed outbecause they reported a major non-adherence to the gluten-free diet. Thus,the study group was confined to 412 patients with self-reportedbiopsy-proven celiac disease who were on a strict gluten-free diet for at least one year. The survey showed that out of these 412 patients that met the criteria, 96 patients, or just over 23% metmodified Rome I criteria for Irritable Bowel Syndrome. Of those 96patients, 76 patients, or nearly 80%, made an effort to get help, bothmedical and non-medical, as a result of the bowel symptoms (we’ll callthe patients who sought help "irritable bowel syndrome patients"). Irritable bowel syndrome-like symptoms were shown to drive SFHS scores sharply downward. Mentalhealth disorders, being female, falling off the gluten-free dietall contributed to a greater likelihood of irritable bowel syndrome symptoms. Theresults of the study seem strengthen the bio-psychosocial model of irritable bowel syndrome, in which biological and psychological factorsare understood to affect the clinical manifestation of celiac disease.Under this model, irritable bowel syndrome-like symptoms in adults withceliac disease are understood through a combination of clinical andsocio-psychological mechanisms. This model leads doctors to anunderstanding of celiac disease and other gastro-intestinal ailmentsthat goes beyond simple biological or psychological factors alone, andlooks at factors like adverse life events, stress, and hypochondriasisamong others. Limited studies indicate that gender differencesin visceral perception, cardio-autonomic responses, gastrointestinalmotility, and brain activation patterns to visceral stimuli are afactor in irritable bowel syndrome. Gender differences in psychosocialfactors have not been fully studied. The results of this studyalso support the need for further investigation to determine exactly whatfactors contribute to the bio-psychosocial model of what is called’celiac irritable bowel syndrome.’ Future psycho-physiologicalstudies in patients with celiac disease and irritable bowel syndromeshould look to determine if psychological discomfort can prolongmucosal inflammation, reduce visceral pain thresholds, or disturb gutmotility. In the event that the right psychotherapeutictreatment for irritable bowel syndrome-like symptoms and/or mentaldisorder serve to improve reduced HRQOL in adult patients with celiacdisease and irritable bowel syndrome-like symptoms, it might benecessary to take a second look at interventional practices. So,in a nutshell, this all means that things like mental health, gender,and other non-clinical factors might play a role in irritable bowelsyndrome-like symptoms in people with celiac disease, and that furtherstudy is needed to sort out all of the possibilities and determine ifthere might be better ways to treat celiac disease that will reduce oreliminate irritable bowel syndrome-like symptoms. Psychosomatic Medicine 69:370 –376 (2007)