One-step immunochromatographic visual assay for anti-transglutaminase detection in organ culture system: An easy and prompt method to simplify the in vitro diagnosis of celiac disease.

BACKGROUND: Anti-tissue transglutaminase (anti-tTG) and endomysium antibodies (EMA) are detectable in duodenal culture media of celiac disease (CD) patients. To improve the management of this organ culture system, we evaluated the anti-tTG occurrence by immunochromatographic assay (ICA). METHODS: A total of 103 CD patients and 41 disease controls underwent duodenal biopsy for the organ culture. In culture supernatants, IgA anti-tTG were tested by both enzyme-linked immunosorbent assay (ELISA) and ICA, IgA EMA were searched by indirect immunofluorescence analysis (iIFA). RESULTS: Endomysium antibodies and anti-tTG measured by ELISA were positive in culture media of all CD patients, while anti-tTG detected by ICA were positive in culture media of 87/103 CD patients. Anti-tTG ICA scores significantly correlated with anti-tTG ELISA values (r=.71, P<.0001). Sensitivity, specificity and diagnostic accuracy of anti-tTG detected by ICA were 84.5%, 100% and 88.9%, respectively. CONCLUSIONS: Using ICA, anti-tTG are detectable in duodenal culture media of most CD patients and the intensity of indicative lines depends on the anti-tTG concentration. Sensitivity and diagnostic accuracy achieved with ICA are lower than those obtained with ELISA but, given that the first is a more easy and prompt method, data suggest the possibility of utilizing it in the in vitro diagnosis of CD.

Are Second Trimester Apparent Diffusion Coefficient Values of the Short Uterine Cervix Associated with Impending Preterm Delivery?

Purpose To prospectively determine whether the apparent diffusion coefficient (ADC) of the cervix is associated with preterm delivery in asymptomatic patients with a sonographic cervical length of 15 mm or less and positive fetal fibronectin test results between 23 and 28 weeks of gestation. Materials and Methods The institutional review board approved this prospective hypotheses-generating study. A total of 30 pregnant women (mean gestational age, 26 weeks) with a sonographic short cervix (≤15 mm) underwent pelvic 1.5-T magnetic resonance (MR) imaging. Oblique sagittal diffusion-weighted images were obtained with b values of 0, 400, and 800 sec/mm(2). ADC values at MR imaging of the subglandular and stromal cervix and the difference between both were correlated to the interval to delivery. Receiver operating characteristic curve analysis was performed to obtain sensitivity and specificity of ADC values in association with delivery within 7 days. Results Eight (27%) of 30 patients delivered within 6 or 7 days after MR imaging (impending delivery group), and 22 (73%) of 30 patients delivered between 18 and 89 days after imaging (mean, 55 days) (late delivery group). Mean subglandular ADC and mean ADC difference were higher (P < .001) in patients with impending delivery than in those with late delivery ([2406.3 ± 166.0] × 10(-6) mm(2)/sec vs [1708.9 ± 108.1] × 10(-6) mm(2)/sec and [657.3 ± 129.9] × 10(-6) mm(2)/sec vs [69.2 ± 70.2] × 10(-6) mm(2)/sec, respectively). Subglandular ADC inversely correlated with the interval between MR imaging and delivery (r = -0.75). Receiver operating characteristic curve analysis of subglandular ADC revealed 100% sensitivity (95% confidence interval: 63.1, 100) and 100% specificity (95% confidence interval: 84.6, 100) in association with impending delivery with a 1921 × 10(-6) mm(2)/sec threshold. Stromal ADC and sonographic cervical length showed no difference between groups (P = .072 and P = .511, respectively). Conclusion Cervical subglandular ADC at MR imaging is associated with impending preterm birth in patients with a short sonographic cervix. (©) RSNA, 2016.

Identification of a serum transglutaminase threshold value for the noninvasive diagnosis of symptomatic adult celiac disease patients: a retrospective study.

BACKGROUND: A celiac disease (CD) diagnosis is based on duodenal histology, with the exception of children showing anti-tissue transglutaminase (anti-tTG) serum levels exceeding ten times the cut-off. Our aim was to reproduce this simplified approach in adults, identifying an anti-tTG threshold value useful to diagnose CD without endoscopic procedures. METHODS: A total of 671 adult CD patients were subjected to blood sampling to determine anti-tTG serum levels, as well as to endoscopy with biopsy to perform duodenal histology. The anti-tTG serum levels/cut-off ratio was compared with the degree of duodenal lesions. RESULTS: Anti-tTG serum levels/cut-off ratio determined in patients with type IIIc was significantly higher than that measured in patients with type IIIb (p < 0.001), IIIa (p < 0.001), II (p < 0.05) and 0 (p < 0.001) of Marsh-Oberhuber histological classification. A significant correlation (r = 0.297, p < 0.0001) was found between the anti-tTG serum levels/cut-off ratio and the degree of duodenal lesions. The anti-tTG serum levels/cut-off ratio was classified as an accurate parameter (AUC = 0.715, p < 0.0001), with the best diagnostic performance obtained considering the threshold value >3.6 (sensitivity = 76.8 %, PPV = 97.2 %). CONCLUSIONS: The anti-tTG serum levels/cut-off ratio correlates with the degree of duodenal lesions and, if used with the threshold value >3.6, could avoid endoscopy with biopsy in about 75 % of seropositive adults waiting for CD diagnosis. However, since this procedure could also imply CD diagnosis in almost 3 % of seropositive patients with normal villous architecture, a consensus opinion is needed to suggest its use in the diagnosis of adult CD.

Nickel-Related Intestinal Mucositis in IBS-Like Patients: Laser Doppler Perfusion Imaging and Oral Mucosa Patch Test in Use.

Nickel (Ni) is often the trigger of irritable bowel syndrome (IBS)-like gastrointestinal disorders: its ingestion may cause allergic contact mucositis, identifiable by means of oral mucosa patch test (omPT). OmPT effectiveness has been proven, but it is still an operator-dependent method. Laser Doppler perfusion imaging (LDPI) was tested to support omPT in Ni allergic contact mucositis diagnosis. Group A: 22 patients with intestinal/systemic symptoms related to the ingestion of Ni-containing foods. Group B: 12 asymptomatic volunteers. Ni-related symptoms and their severity were tested by a questionnaire. All patients underwent Ni omPT with clinical evaluation at baseline (T0), after 30 min (T1), after 2 h (T2), and after 24-48 h (T3). LDPI was performed to evaluate the mean mucosal perfusion at T0, T1, and T2. Statistical analysis was performed by ANOVA test and Bonferroni multiple-comparison test. All 22 Ni-sensitive patients (group A) presented oral mucosa hyperemia and/or edema at T2. Eight out of the same 22 patients presented a local delayed vesicular reaction at T3 (group A1), unlike the remaining 14 out of 22 patients (group A2). All 12 patients belonging to control group B did not show any alteration. The mean mucosal perfusion calculated with LDPI showed an increase in both subgroups A1 and A2. In group B, no significant perfusion variations were observed. LDPI may support omPT for diagnostic purposes in Ni allergic contact mucositis. This also applies to symptomatic Ni-sensitive patients without aphthous stomatitis after 24-48 h from omPT and that could risk to miss the diagnosis.

Diagnosis of Small-Bowel Diseases: Prospective Comparison of Multi-Detector Row CT Enterography with MR Enterography.

PURPOSE: To prospectively compare the accuracies of computed tomographic (CT) enterography and magnetic resonance (MR) enterography for the detection and characterization of small-bowel diseases. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained from all participants. From June 2009 to July 2013, 150 consecutive patients (81 men and 69 women; mean age, 38.8 years; range, 18-74 years), who were suspected of having a small-bowel disease on the basis of clinical findings and whose previous upper and lower gastrointestinal endoscopy findings were normal, underwent CT and MR enterography. Two independent readers reviewed CT and MR enterographic images for the presence of small-bowel diseases, for differentiating between inflammatory and noninflammatory diseases, and for extraenteric complications. The histopathologic findings of surgical (n = 23) and endoscopic (n = 32) biopsy specimens were used as the reference standard; the results of video-capsule endoscopy (n = 36) and clinical follow-up (n = 59) were used only to confirm the absence of small-bowel disease. RESULTS: MR and CT enterography were successfully performed in all 150 patients. Overall sensitivity, specificity, and accuracy, respectively, in identifying patients with small-bowel lesions were 75.9% (41 of 54), 94.8% (91 of 96), and 88.0% (132 of 150) for CT enterography and 92.6% (50 of 54), 99.0% (95 of 96), and 96.7% (145 of 150) for MR enterography. The sensitivity of MR enterography was significantly higher than that of CT enterography for the detection of both overall small-bowel diseases (P = .0159) and neoplastic diseases (P = .0412) but not for the detection of inflammatory diseases (P > .99) or noninflammatory and nonneoplastic diseases (P = .6171). CONCLUSION: MR enterography is more accurate than CT enterography in the detection of small-bowel diseases; MR enterography was more accurate in detecting neoplastic diseases in particular.

Extension of the celiac intestinal antibody (CIA) pattern through eight antibody assessments in fecal supernatants from patients with celiac disease.

BACKGROUND: Detection of anti-transglutaminase, anti-endomysium and anti-gliadin antibodies is commonly used to screen celiac disease patients. Besides that in serum, these antibodies are detectable in culture supernatants of oral, duodenal and colonic biopsy samples, saliva, gut lavage fluid samples, and fecal supernatants. Our aim was to extend the intestinal antibody pattern in fecal supernatants from patients with celiac disease. METHODS: The fecal supernatants obtained from 25 celiac disease patients and 12 healthy volunteers were used to determine IgA and IgG1 anti-endomysium by immunofluorescence analysis, IgA and IgG anti-transglutaminase, IgA and IgG anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin by enzyme-linked immunosorbent assay. RESULTS: IgA anti-endomysium were found in 11 of 25 (44.0%) celiac disease patients and in none of healthy volunteers (p=0.0066). The levels of IgA anti-transglutaminase, IgA anti-deamidated gliadin peptides, IgA/IgG anti-transglutaminase/deamidated gliadin peptides and IgA anti-actin determined in celiac disease patients were significantly higher (p=0.0005, p=0.0018, p=0.0061 and p=0.0477, respectively) than those measured in healthy volunteers. The ROC curve analysis showed a diagnostic significance in IgA anti-transglutaminase (AUC=0.862, p<0.0001), IgA anti-deamidated gliadin peptides (AUC=0.822, p<0.0001) and IgA/IgG anti-transglutaminase/deamidated gliadin peptides (AUC=0.783, p=0.0003) fecal tests. CONCLUSIONS: Our data extend the intestinal antibody pattern detectable in fecal supernatants, thus increasing the knowledge in the humoral immunity of celiac disease. Further studies are needed to better evaluate the role of fecal antibody tests in identifying celiac disease patients.

Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios.

INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. AIM: We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. RESULTS: Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. DISCUSSION: Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.

Mutatis mutandis: are we diagnosing too many people with non-celiac gluten sensitivity? Multiple case report.

We report three patients presenting with gluten-related signs and symptoms. Since villous height/crypt depth ratio, intraepithelial lymphocyte count, and serum antibody tests were not diagnostic for celiac disease (CD), a diagnosis of non-celiac gluten sensitivity (NCGS) was suggested. On the other hand, antibodies suggestive for CD surprisingly showed positive results in the duodenal biopsy organ culture of all three cases. The reported cases suggest the precious potential role that organ culture systems may play in differentiating CD from NCGS. This method should be recommended when gluten-related disorders are suspected in order to reduce the inappropriate diagnosis of NCGS.

Peripheral blood lymphocyte typing as a useful tool to objectify the oral mucosa patch test in the diagnosis of allergic contact mucositis to nickel.

Nickel (Ni) exposure through the intestinal mucosa may cause a hypersensitivity reaction recently defined as allergic contact mucositis (ACM). This condition is identifiable by the oral mucosa patch test (omPT), a qualitative and subjective examination that requires clinical expertise. Our aim was to evaluate if a peripheral blood lymphocyte typing performed before and after the omPT for Ni may be able to objectify this examination for diagnostic purposes. Thirty patients with symptoms referable to the ingestion of Ni-rich foods were subjected to omPT for Ni. Before and after the omPT, each patient underwent blood sampling for the typing of total lymphocytes and their subsets (T, T helper or Th, T cytotoxic or Tc, B, natural killer or NK). Statistical analysis was performed by Student t test and receiver operating characteristic (ROC) curve analysis. According to the omPT outcomes, 18 patients were defined as Ni-sensitive and the remaining 12 as controls. In Ni-sensitive patients, the number of total, T, Th, Tc, and B lymphocytes/µL whole blood increased after the omPT (p<0.0001 for the first three, p=0.0004 and p=0.0001 for the last two lymphocyte types). No omPT-dependent lymphocyte increase was observed in controls. The post/pre omPT cell ratio, especially if calculated for Th lymphocytes, appears to be an effective index for diagnostic purposes (sensitivity=100%, specificity=83.3%, Youden index=0.833, area under curve (AUC)=0.926, p<0.0001). In conclusion, the peripheral blood lymphocyte typing with calculation of post/pre omPT cell ratio has the potential to support the omPT in diagnosing ACM, with the advantage of providing quantitative and objective data.

Immunological characterization of the allergic contact mucositis related to the ingestion of nickel-rich foods.

BACKGROUND: The ingestion of nickel (Ni)-rich foods may result in allergic contact mucositis (ACM), a not yet well defined condition identifiable by oral mucosa patch test (omPT). Our aim was to characterize immunologically the ACM taking advantage from the allergen exposure that occurs during the omPT for Ni. METHODS: Thirty-seven symptomatic patients underwent to omPT for Ni. Before and after omPT, serum and urine Ni concentrations were determined by mass spectrometry, the white blood cells were counted by hemochromocytometric assay, the peripheral lymphocyte typing was carried out by flow cytometry, total IgE and cytokine serum concentrations were measured by immunoenzymatic assays. The local lymphocyte typing was performed by immunohistochemistry only after omPT. RESULTS: According to the omPT outcomes, 25 patients were defined as Ni-sensitive and the remaining 12 as controls. After omPT, serum and urine Ni concentrations increased significantly in all patients, while a significant increment of circulating lymphocytes and neutrophils was highlighted, respectively, in Ni-sensitive and control patients. Consistently, the Th and Tc circulating lymphocytes, as well as the Th/Tc ratio increased significantly in Ni-sensitive patients after omPT. No noteworthy increment in serum concentrations of total IgE and selected cytokines was observed in any patient after omPT. The presence of CD3+, CD4+, and CD8+ cells was highlighted on the oral mucosa biopsy samples taken from Ni-sensitive patients after omPT. CONCLUSIONS: In patients with ACM, a local adaptive response with increased lymphocyte trafficking appears to be the most likely mechanism of reaction to Ni administered with the omPT.

Colonic involvement in celiac disease and possible implications of the sigmoid mucosa organ culture in its diagnosis.

PURPOSE: Celiac disease (CD), a systemic autoimmune disorder that typically involves duodenal mucosa, can also affect other intestinal areas. Duodenal and oral mucosa organ culture has already been demonstrated as a reliable procedure to identify CD. The present study investigated gluten-dependent immunological activation of colonic mucosa in CD patients. We took advantage of the numerous colonoscopies performed for various clinical conditions or only for defensive medicine. METHODS: Forty-four patients with gastrointestinal symptoms or in need of colorectal cancer screening were divided into patients with serum anti-endomysium (EMA) and anti-tissue transglutaminase (anti-tTG) antibody positive results (Group A), patients with serum antibody negative results (Group B), and patients with inflammatory bowel disease (IBD) (Group C). The autoantibodies EMA and anti-tTG were evaluated in supernatants of cultured sigmoid and duodenal biopsies from patients on a gluten-containing diet. RESULTS: In Group A, EMA and anti-tTG resulted positive in all duodenal culture supernatants. In sigmoid culture supernatants, EMA and anti-tTG were detected in 12/16 (75 %) and 13/16 (81.3 %) patients, respectively. In Group B, none of the 17 patients showed EMA and anti-tTG positive results in both duodenal and sigmoid cultures. In Group C, all 11 patients presented EMA negative results in sigmoid cultures. Only in one patient, anti-tTG were detectable in the sigmoid culture supernatant, as expected in cases of IBD. CONCLUSIONS: Data confirm that the gluten-dependent immunological activation affects more intestinal tracts with different degrees of involvement, suggesting that the organ culture of colonic biopsies could represent a new tool to opportunistically detect CD.

Usefulness of the organ culture system when villous height/crypt depth ratio, intraepithelial lymphocyte count, or serum antibody tests are not diagnostic for celiac disease.

The existence of mild forms of celiac disease (CD) can make the histology-based diagnosis difficult to reach. Since anti-endomysium (EMA) and anti-tissue transglutaminase (anti-tTG) are detectable in culture supernatants of duodenal biopsies from CD patients, our aim was to assess if this system can support the histology in the diagnostic work-up. A total of 559 suspected CD patients underwent serum EMA/anti-tTG detection, upper endoscopy with duodenal biopsy sampling, histologic analysis, and organ culture to detect EMA/anti-tTG in supernatants. A subgroup of 30 patients with organ culture positive results were put on a gluten-free diet (GFD). Their gluten-dependency was evaluated by the psychological general well-being and beck depression inventory indexes. Statistical analysis was performed by Cohen k inter-test, Friedman test, and Dunn multiple comparison. Two hundred forty-one out of 559 (43.1%) patients showed intestinal villous atrophy, whereas serum and organ culture EMA/anti-tTG were positive in 293/559 (52.4%) and 334/559 (59.7%) patients, respectively. The strength of agreement resulted good for serology vs histology (k = 0.730), good for organ culture vs histology (k = 0.662), and very good for serology vs organ culture (k = 0.852). After 12 months of GFD, psychological general well-being index significantly increased, and beck depression inventory index significantly decreased (P < 0.001 for each one). Data highlight the organ culture system as a useful tool to assist the histology in diagnosing CD, mainly in cases without villous atrophy or in seronegative patients. The marked improvement in quality of life after a GFD further supports the reliability of this system in diagnosing CD.

Oral mucosa patch test: a new tool to recognize and study the adverse effects of dietary nickel exposure.

On contact with the skin, nickel may cause allergic contact dermatitis, which can be diagnosed by an epicutaneous patch test. Nickel exposure via the intestinal mucosa can induce diarrhea, abdominal pain, and swelling. The aim of the present study was to investigate the relationship between these symptoms and nickel intake by means of a novel oral mucosa patch test. Eighty-six patients with intestinal symptoms related to ingestion of nickel-containing foods were submitted to epicutaneous and oral mucosa patch tests for nickel. All patients with positive oral mucosa patch test results were subject to a low-nickel diet and monitored over time. Skin lesions were observed in 33 out of 86 (38.4%) patients evaluated by the epicutaneous patch test. Mucosal lesions were seen in 53 out of 86 (61.6%) patients given the oral mucosa patch test. After 2 months of a low-nickel diet, 52 out of 53 (98.1%) patients showed an improvement of their symptoms. There is a significant correlation between response time of the oral mucosa patch test and the latency of symptoms after ingestion of nickel-containing foods. Consequently, the oral mucosa patch test can be used to recognize and study the adverse effects of dietary nickel exposure that could be defined as allergic contact mucositis. A low-nickel diet is also shown to be an effective treatment for this condition.

Celiac disease: evaluation with dynamic contrast-enhanced MR imaging.

PURPOSE: To prospectively determine mural perfusion dynamics in patients with untreated celiac disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to compare these dynamics with those in a control population and in patients with celiac disease treated with a gluten-free diet. MATERIALS AND METHODS: Institutional review board approval and informed consent from all participants were obtained. Sixty consecutive patients with untreated celiac disease, 45 patients with celiac disease treated with a gluten-free diet for at least 1 year, and 30 control subjects were enrolled in this study. Dynamic contrast-enhanced MR imaging was performed by using a 1.5-T MR unit. For each MR imaging examination, maximum enhancement, slope of enhancement, and time-signal intensity curves were calculated at the level of the descending duodenal wall. Duodenal wall thickness was also evaluated. Statistical evaluation was performed by using one-way analysis of variance, and the results were confirmed by using the Bartlett test for equal variances and complemented by using Bonferroni multiple comparison, linear correlation, and the Student t test for paired data. RESULTS: Mean maximum enhancement of the duodenal wall was significantly higher in patients with untreated celiac disease (229.1 +/- 46.4 [standard deviation]) than in patients with treated celiac disease (109.8 +/- 27.8) and control subjects (94.7 +/- 17.9) (P < .001 for each comparison). All 60 untreated patients showed a curve characterized by fast enhancement and washout (type 4), while all 45 treated patients and the 30 control subjects showed a curve characterized by slow constant enhancement (type 2). Mean duodenal wall thickness was not significantly different between untreated patients (2.2 mm +/- 0.4), treated patients (2.0 mm +/- 0.3), and control subjects (2.0 mm +/- 0.4) (one-way analysis of variance, P = .4177; Bartlett test, P = .6951). CONCLUSION: The results of this study suggest that dynamic evaluation of the bowel wall by using contrast-enhanced MR imaging can be an effective and reproducible way to show the inflammation state in celiac disease.

High incidence of celiac disease in patients with systemic sclerosis.

OBJECTIVE: To evaluate the presence of celiac disease in patients with systemic sclerosis (SSc). The association of autoimmune diseases with celiac disease has been reported, but few publications deal with the combination of SSc and celiac disease. METHODS: We investigated the presence of anti-tissue transglutaminase (anti-tTG) antibodies and serum antiendomysial antibodies (anti-EMA) in 50 patients with SSc. All subjects were on a gluten-containing diet. Duodenal mucosa histology and biopsy culture were performed in anti-tTG-positive patients; anti-EMA and IgA, IgG1 anti-tTG were detected in culture supernatants. RESULTS: The incidence of celiac disease in patients with SSc was found to be 8%. Serum anti-tTG antibody-positive results were detectable in 5 out of 50 patients with SSc, but only in 4 of them was the diagnosis confirmed by histological results (Marsh classification). CONCLUSION: Our data show an increased prevalence of celiac disease in patients with SSc.

Adult celiac disease: what is the role of MRI?

PURPOSE: To evaluate the ability of MRI to identify intra- and extraintestinal findings of celiac disease in an adult population. MATERIALS AND METHODS: Forty-one subjects (18 men and 23 women; mean age = 41.3 years; 31 with biopsy-proven celiac disease, and 10 healthy volunteers) underwent MRI of the small bowel. MR studies were performed on a 1.5-T magnet using T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) and true fast imaging in steady-state precession (True-FISP) sequences. The MR features and sensitivity, and the specificity and accuracy of some of these features are described. RESULTS: In the 31 celiac patients, MRI showed bowel dilatation in 61.3% (N = 19), increased number of ileal folds in 48.4% (N = 15), reversed fold pattern abnormality in 38.7% (N = 12), increased wall thickness in 16.1% (N = 5), duodenal stenosis in 6.5% (N = 2), intussusception in 12.9% (N = 4), mesenteric lymphadenopathy in 41.9% (N = 13), mesenteric vascular changes in 22.6% (N = 7), ascites in 6.5% (N = 2), and no abnormalities in 12.9% (N = 4). The volunteers had unremarkable exams. The overall specificity and accuracy were 100%, and sensitivity was 79% and 75% for increased number of ileal folders and reversed fold pattern abnormality, respectively. CONCLUSION: MRI is able to demonstrate intra- and extraintestinal features that may lead to the diagnosis of celiac disease in adults.

Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: a multicentre study.

OBJECTIVE: Diagnosis of coeliac disease is based on the presence of villous atrophy which recovers following a gluten-free diet. The presence of circulating antiendomysial antibodies as well as their disappearance after a gluten-free diet supports the diagnosis. It has also been demonstrated that antiendomysial antibodies are detectable in supernatants of cultured intestinal biopsies from patients with coeliac disease. The objective of this study was to compare the histology and antiendomysial antibodies in culture supernatants of intestinal biopsies to validate the in vitro organ culture system as a future diagnostic tool for coeliac disease. MATERIAL AND METHODS: Seventy-five antiendomysial serum-positive patients on a gluten-containing diet were evaluated. Patients underwent endoscopy with 5 biopsy fragments: 3 for histology, 1 cultured with and the other without gliadin-peptide activator. Antiendomysial antibodies were evaluated in all culture supernatants. RESULTS: Sixty-eight patients had evidence of villous atrophy, while 73 out of 75 were positive to the organ culture system. The agreement rate between organ culture and histology results was 94%. CONCLUSIONS: As all the centres participating in the study obtained good agreement between organ culture and histology results, the new system could be considered a reliable tool for the diagnosis of coeliac disease. Nevertheless, it is possible to highlight cases with an organ culture-positive and -negative histology. This feature could be of considerable interest because, as the sensitivity of organ culture seems to be greater than the initial histology, the new system might be useful in uncertain cases where the risk of missing the diagnosis of coeliac disease is high.

Antiendomysial antibody detection in biopsy culture allows avoidance of gluten challenge in celiac children.

OBJECTIVE: Antiendomysial antibody (EMA) production has been induced in vitro by the small bowel mucosa of celiac disease (CD) patients in clinical remission cultured in the presence of gliadin peptides. The aim of the present study was to use this in vitro system to determine whether it could be used to predict the clinical or histologic relapse to gluten challenge in CD children on a gluten-free diet (GFD). METHODS: Enrolled were 32 CD children and adolescents on GFD (group 1), and 80 controls (group 2) who underwent in vitro gliadin challenge. Subsequently, 24 group 1 CD children underwent in vivo gluten challenge to confirm the diagnosis. Biopsy cultures, with and without gliadin, morphometric analysis, immunoglobulin (Ig)A and IgG1 EMA detection, both in sera and culture supernatants, were performed. RESULTS: Of the 32 group 1 CD patients, 23 were IgA EMA positive in culture supernatants. The other nine were IgG1 EMA positive. All 24 children who had in vivo gluten challenge showed clinical or histologic relapse. All culture supernatants from disease controls belonging to group 2 were both IgA and IgG1 EMA negative, irrespective of gliadin challenge. CONCLUSIONS: Organ culture with in vitro gliadin challenge is able to reproduce the results of in vivo challenge. This system could reduce the need for gluten challenge in celiac children.

Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence.

Anti-tissue transglutaminase, previously held to be identical to anti-endomysial antibodies in celiac sprue, has been reported in inflammatory bowel disease patients. To investigate these data further, we evaluated serum and intestinal anti-tissue transglutaminase in inflammatory bowel disease patients, with respect to the Crohn's disease activity index and the integrated disease activity index. Study population comprised: 49 patients with Crohn's disease and 29 patients with ulcerative colitis; 45 patients with celiac sprue and 85 autoimmune patients as disease controls; and 58 volunteers as healthy controls. Immunoglobulin A (IgA) anti-recombinant human tissue transglutaminase and anti-endomysial antibody detection in sera and fecal supernatants were performed. Adsorption of positive sera with recombinant human tissue transglutaminase were also performed. Marked increased anti-tissue transglutaminase concentrations were found in celiac sprue, while low-positive values were also found in Crohn's disease and ulcerative colitis. Anti-endomysial antibodies were detectable only in celiac sprue. Antigen adsorption resulted in a significant reduction of the anti-tissue transglutaminase either in celiac sprue or inflammatory bowel disease sera. A significant correlation between anti-tissue transglutaminase and Crohn's disease activity index or integrated disease activity index scores was found. Anti-tissue transglutaminase was also detectable in fecal supernatants from inflammatory bowel disease patients. Data highlight that both circulating and intestinal anti-tissue transglutaminases are detectable in inflammatory bowel disease, and that they are related to disease activity. These features underline that, in addition to anti-tissue transglutaminase, an anti-endomysial antibody test is necessary in the diagnostic work-up of celiac sprue, especially in patients with known inflammatory bowel disease.

Antiendomysial antibodies in Berger's disease.

The finding of increased levels of immunoglobulin A (IgA) against food antigens in patients with IgA nephropathy prompted the hypothesis of an association between IgA nephropathy and celiac disease (CD). Attention was initially directed to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1-EMA have been found in patients with CD with IgA-EMA-negative results. The presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect immunofluorescence analysis. At the time of renal biopsy, the following factors were evaluated: history of macroscopic hematuria, serum creatinine level, urinalysis, 24-hour proteinuria, blood pressure, and histological classification of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were positive for both isotypes. No significant differences were observed between the two groups (EMA positive versus EMA negative) concerning age, serum creatinine level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of renal histological involvement. IgA- and IgG1-EMA were not detected in patients with other primary nephropathies or lupus nephritis. These results, based on the finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be investigated in patients with IgA nephropathy. Furthermore, the role of a gluten-free diet in the natural history of IgA nephropathy, at least in EMA-positive patients, needs to be ascertained.