Murray, Joseph A.

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.

Abstract We have investigated the genetic basis of the immune response to dietary gluten in HCD4/DQ8 and HCD4/DQ6 double transgenic mice. Mice were immunized with gluten i.p. or individual peptides s.c. and spleen or draining lymph node T cells were challenged in vitro. Strong proliferative responses to gluten were seen in the HCD4/DQ8 mice, whereas the HCD4/DQ6 mice responded to gluten poorly. A series of overlapping peptides spanning gliadin were synthesized. The HCD4/DQ8 mice reacted to many of the individual peptides of gliadin, while the HCD4/DQ6 mice were relatively unresponsive. T cells isolated from HCD4/DQ8 mice also responded well to modified (deamidated) versions of the gliadin peptides, whereas HCD4DQ6 mice did not. The T cell response to gluten was CD4 dependent and DQ restricted and led to the production of cytokines IL-6, TGF-β, and IL-10. Finally, intestinal lymphocytes isolated from gluten-fed HCD4/DQ8 mice displayed an activated phenotype. These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease.

ABSTRACTObjectives:Limited data suggest complete mucosal healing in treated children with celiac disease (CD), but recent data from adult endoscopic biopsies have shown substantial numbers with persistent mucosal injury. We aimed to assess the rate of mucosal healing and indications for repeat small bowel (SB) biopsy in children with CD.Methods:We retrospectively reviewed records of children (ages 1–18 years) with CD who underwent a second SB biopsy. All of the children were seen at Mayo Clinic (Rochester, MN) from January 1997 through June 2013.Results:Forty children were identified (14 boys); average age at diagnosis was 8.5 years. Indications for second SB biopsy were abdominal pain (n = 20), diarrhea (n = 7), constipation (n = 5), non–celiac‐related concern (n = 2), follow‐up (n = 5), and persistent serology (n = 1). Average time between biopsies was 24 months (range 4–120 months). Histology on the second biopsy showed complete healing (n = 25), intraepithelial lymphocytes (n = 9), and persistent villous atrophy (n = 6). Of these, 3 patients had partial villous atrophy and 3 had with complete villous atrophy. Persistent villous atrophy was observed in 2 of 20 patients with abdominal pain and 1 of 7 with diarrhea. All of the patients with persistent constipation (n = 5) had complete resolution.Conclusions:Mucosal healing in children with CD may not be complete as previously assumed. Abdominal pain was the most common indication for repeating the SB biopsy. Persistence of abdominal pain, diarrhea, and constipation was poorly associated with persistence of mucosal injury.

ABSTRACTBackground:The purpose of this study was to identify the frequency of fat‐soluble vitamin deficiencies in children with celiac disease (CD) and to determine the value of routine testing for these deficiencies.Methods:We conducted a retrospective medical record review of patients with a confirmed diagnosis of CD and fat‐soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic. Patients' demographics, fat‐soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected.Results:Eighty‐three patients were included in the final analysis: 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys. The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of CD was reported in 32 patients. Average vitamin levels for vitamin E, 25‐hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 μg/dL, respectively. No patients had vitamin A deficiency, 2 patients had vitamin E deficiency, and 9 patients had mild‐to‐moderate vitamin D deficiency (none had severe deficiency). Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy. Thirty‐one patients had insufficiency of 25 (OH) D, which was less than the reported frequency of vitamin D insufficiency in the general pediatric population in the United States in 2004. None of the patients were receiving vitamin supplements at the time of diagnosis.Conclusions:Fat‐soluble vitamin deficiencies are uncommon in children with new diagnosis of CD. Routine measuring of fat‐soluble vitamins levels may not be necessary.

SummaryBackgroundVillous atrophy (VA) with intraepithelial lymphocytosis is the histological hallmark of coeliac disease (CD), but reported rates of mucosal recovery are variable.AimTo determine the impact of age and other demographic variables on the probability of persistent VA on follow‐up biopsy.MethodsWe identified patients with VA on duodenal histology at all 28 Swedish pathology departments during the years spanning 1969–2008. We examined age, gender, calendar period, duration of disease and educational attainment to determine predictors of persistent VA.ResultsOf 7648 patients with CD who underwent follow‐up biopsy, persistent VA was present in 3317 (43%; 95% CI 42–44%). The effect of age on persistent VA varied according to time period; among those biopsied in the years spanning 2000–2008, the prevalence of persistent VA was 31%, and increasing age was associated with increasing rates of persistent VA (17% among those younger than 2 years compared to 56% among those ≥70 years). In contrast, persistent VA did not vary widely by age in earlier years. On multivariate analysis (restricted to the calendar period 2000–2008, 2–5 years after CD diagnosis), persistent VA was more common among males (OR 1.43; 95% CI 1.07–1.90) and less common among patients with higher educational attainment (OR for college degree vs. <2 years of high school 0.52, 95% CI 0.35–0.78).ConclusionsThe prevalence of persistent villous atrophy has changed over time, with greater rates of healing in recent years. Social differences in persistent villous atrophy suggest that access and/or education regarding the gluten‐free diet impact mucosal healing.

Significance The diagnosis of many diseases is dependent upon accurate detection of particular antibodies present in blood. However, the development of biochemical reagents that can reliably detect these antibodies has proved remarkably challenging. This study describes a process to create biochemical reagents that can accurately and reliably detect disease-associated antibodies, without requiring knowledge of the cause or mechanisms of disease. Simultaneously, this process enabled identification of a critical environmental agent involved in celiac disease. Thus, the process presented here may enable the development of effective diagnostic tests for other medical conditions where such tests are lacking and the identification of environmental factors involved in disease.