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Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 06/10/2016 - Do all patients with potential celiac disease need a gluten-free diet? The transformation of potential celiac disease to full-blown celiac disease has been described in some western clinical studies, but there is no good data on cases in Asia. Recently, a team of researchers set out to study the short-term histological course of potential celiac disease in Indian patients. The research team included R Kondala, AS Puri, AK Banka, S Sachdeva, and P Sakhuja. They are variously affiliated with the Department of Gastroenterology and the Department of Pathology at Govind Ballabh Pant Hospital, New Delhi, India. For their study, the team identified prospective patients with potential celiac disease by screening relatives of celiac patients, patients with the diarrheal subtype of irritable bowel syndrome (IBS-D) and patients with iron deficiency anemia (IDA). They conducted endoscopy with duodenal biopsy on patients who tested positive for immunoglobulin A antibodies against tissue transglutaminase (IgA anti-tTG) Patients a Marsh-0 to Marsh-II lesion on duodenal biopsy, along with positive IgA tTG serology met the definition of celiac disease. The team retested for serology and histology at 6-month and 12 months. The team diagnosed 23 male and 34 female patients with potential celiac disease. Patients ranged from 4-73 years old, averaging 28.7 years. Of these 57 patients, 28 were identified by screening 192 first-degree relatives of 55 index cases of celiac disease, while the remaining 29 had either IBS-D or IDA. Duodenal biopsy showed Marsh-0, Marsh-I and Marsh-II changes in 28 celiac patients, 27 IBS-D patients, and 2 IDA patients. After 6 months, 12 patients became seronegative, while the remaining 45 patients continued to be seropositive at the 12-month time point. Only four patients moved to Marsh III status, while progression from Marsh-0 to either Marsh-I or Marsh-II occurred in six patients and one patient, respectively. Meanwhile, 14 patients with Marsh-I did show regression to Marsh-0. Of the two patients who were initially Marsh-II, one remained so upon follow up and one showed favorable regression to Marsh-0 status. This study shows that, even though almost 80% of the patients diagnosed have potential celiac disease continue to remain seropositive for tTG 12 months later, only 7% slipped to Marsh-III over the same time period. According to this team, these observations do not justify starting a gluten-free diet in all patients with potential celiac disease, in India. With all due respect to the research team, I wonder what would happen to these patients if they were followed over a greater time span? Would their conditions worsen? Clearly some longer term follow-up of such patients is warranted. Also, how many such patients would see an even greater regression of their symptoms and Marsh status if they followed a gluten-free diet? This study doesn’t tell us much about the possible benefits of a gluten-free diet in cases of potential celiac disease, just that, absent a gluten-free diet, some patients worsen and some improve. Source: United European Gastroenterol J. 2016 Apr;4(2):275-80. doi: 10.1177/2050640615594935.
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 06/01/2016 - People with potential celiac disease (PCD) have blood and genetic markers for celiac disease, but show little or no damage to the small intestinal mucosa. A research team recently conducted a prospective study to learn more about how the disease progresses in these individuals. The research team included U Volta, G Caio, F Giancola, KJ Rhoden, E Ruggeri, E Boschetti, V Stanghellini, and R De Giorgio. They are all affiliated with the departments of Medical and Surgical Sciences and Digestive System, Centro di Ricerca Biomedica Applicata at the University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy. For their study the team collected data from 59 women and 18 men, averaging 33 years of age. The patients were all diagnosed with potential celiac disease, based on blood tests and HLA type, at Bologna University in Italy from 2004 through 2013. All patients had either slight inflammation of the small intestinal mucosa, or normal mucosa. The team assessed clinical, laboratory, and histologic parameters at diagnosis and during a 3-year follow-up period. Forty-six female and 15 male patients, with an average age of 36 years, showed intestinal and extra-intestinal symptoms, whereas the remaining 13 female and 3 male patients, averaging 21 years of age, showed no symptoms at diagnosis. All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients carried the HLA-DQ2 gene. Duodenal biopsies showed that 26% of patients had a Marsh score of 0, while 74% had a Marsh score of 1. Thirty-six percent of symptomatic patients had autoimmune disorders, and 41% had antinuclear antibodies, compared to just 5% and 12% asymptomatic patients, respectively. Symptomatic patients were generally older at diagnosis (P < .05). Gluten-free diet led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable. This 3-year study of adults with potential celiac disease shows that most do have symptoms, which improved on gluten-free diet. However, asymptomatic adults with potential celiac disease do not tend to develop villous atrophy, and so do not require treatment with a gluten-free diet. Source: Clin Gastroenterol Hepatol. 2016 May;14(5):686-693.e1. doi: 10.1016/j.cgh.2015.10.024. Epub 2015 Oct 30.
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 09/03/2014 - What’s potential celiac disease, and what happens to kids who have it and continue to eat a gluten-containing diet? Researchers define potential celiac disease as the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies with normal duodenal mucosa. That is, a positive blood screen, but no intestinal damage. However, not much is known about potential celiac disease because people who have it often show no obvious symptoms. Patients with potential celiac disease present some challenges for doctors trying to determine how likely it is that these patients will develop villous atrophy, the gut damage common in celiac disease patients exposed to gluten. A research team conducted a prospective longitudinal cohort study to follow patients with potential celiac disease up to 9 years, and explore the risk factors tied to mucosal damage. The research team included Renata Auricchio MD, PhD, Antonella Tosco MD, Emanuela Piccolo MD, Martina Galatola PhD, Valentina Izzo PhD, Mariantonia Maglio PhD, Francesco Paparo PhD, Riccardo Troncone MD, PhD, and Luigi Greco MD, PhD. They are affiliated with the Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy. For their study, the team found two hundred and ten asymptomatic children with potential celiac disease. They kept 175 of them on a gluten-containing diet. To evaluate histological, immuno-histochemical, and anti-TG2 status, they checked blood antibody levels and clinical symptoms every 6 months, and took a small bowel biopsy every two years. They also genotyped all patients for HLA and non-HLA celiac-associated genes. Forty-three percent of patients showed persistently elevated anti-TG2 levels, 20% became negative during follow-up, and 37% showed variations in anti-TG2 course, with many patients testing at zero anti-TG2. After three years of follow-up, 86% of study patients continued to have potential celiac disease. After 6 and 9 years, respectively, 73% and 67% of study patients still had normal duodenal structure. Individuals prone to develop mucosal damage during the test period were predominantly male, had slight mucosal inflammation at study’s start, and fit a peculiar genetic profile. Nine years after follow-up, a large number of patients with asymptomatic potential celiac disease showed reduced antibody production, many even showing zero production, and many of these, with persistently positive anti-TG2, showed no mucosal damage. Given the results of this study, and noting that the celiac population is in fact made up of numerous individuals with diverse genetic and phenotypic makeup, the researchers are advising doctors to be cautious in prescribing a strict lifelong gluten-free diet for asymptomatic individuals with potential celiac disease. Source: The American Journal of Gastroenterology
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 08/15/2011 - People with potential celiac disease have similar HLA, and positive anti-transglutaminase antibodies, but do not suffer damage to small intestinal mucosa. Very few of these patients develop mucosal lesions. So far, scientists know of more than forty genes associated with celiac disease, but exactly how these pathways act to trigger celiac disease in genetically predisposed individuals remains a mystery. A team of researchers recently set out to shed some light on that mystery. The research team included Maria Pia Sperandeo, Antonella Tosco, Valentina Izzo, Francesca Tucci, Riccardo Troncone, Renata Auricchio, Jihane Romanos, Gosia Trynka, Salvatore Auricchio, Bana Jabri, and Luigi Greco. They are variously affiliated with the European Laboratory for Food Induced Disease, and the Department of Pediatrics at the University of Naples Federico II in Naples, Italy, the Department of Genetics at the University Medical Centre at the University of Groningen, Groningen in The Netherlands, and with the Department of Medicine, the Department of Pathology and the Department of Pediatrics at University of Chicago. To more fully explore the genetic features of potential celiac disease individuals, the team enrolled 127 patients with potential celiac disease, positive anti-tissue transglutaminase and no mucosal lesions. Ultimately, about 30% of those followed for four years developed celiac disease. The team then genotyped each of the subjects for 13 polymorphisms of the 'candidate genes’ and compared the results to control subjects, and to patients with known celiac disease. They used 60 biopsy specimens to more fully evaluate gene expression. They found that people with potential celiac disease have less HLA-related risk compared to those with celiac disease (Ï‡2 = 48.42; p value = 1Ã—10âˆ’8). Those with potential celiac disease also share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (Ï‡2 = 5.42; p value = 0.02). There was one marker of the KIAA1109/IL-2/IL-21 region that differentiated those with potential celiac disease from those with clinical celiac disease (rs4374642: Ï‡2 = 7.17, p value = 0.01). In people with potential celiac disease, the expression of IL-21 was completely suppressed, whereas, in those with celiac disease (p value = 0.02) and in control subjects (p value = 0.02), IL-2, KIAA1109 and c-REL expression were over-expressed. The study reveals that people with potential celiac disease show different genetic features expression markers than those with celiac disease. The study also shows potential celiac disease to be a useful biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals. Source: PLoS ONE 6(7): e21281. doi:10.1371/journal.pone.0021281