Under the umbrella of coeliac disease (CD), or gluten‐sensitive enteropathy, the concepts of silent, latent and potential CD have recently been introduced. While silent CD is marked by severe damage to the jejunal mucosa in the absence of clinical symptoms, both latent and potential CD are characterized by a jejunal mucosa that would be reported as normal by most clinical pathologists in an individual on a gluten‐containing diet. As opposed to potential coeliac patients, latent subjects sometime in their life have had a flat jejunal biopsy which recovered on a gluten‐free diet. Latent coeliac patients are often symptomatic; neither high titres of gliadin antibodies nor mucosal changes (including raised intraepithelial lymphocyte counts) are obligate features of latent CD, although the presence of elevated endomysial antibodies is probably the best predictor of progression towards villous atrophy. The term potential CD has been proposed for those subjects who do not have, and have never had, a jejunal biopsy consistent with overt CD, and yet have immunological abnormalities similar to those found in coeliac patients. Good markers of potential CD include the presence of serum endomysial antibodies, a high count of intraepithelial lymphocytes and subtle pathological alterations such as increased density of intraepithelial lymphocytes expressing γδ T cell receptor, signs of activated mucosal cell‐mediated immunity, coeliac‐like intestinal antibody pattern, and positive rectal gluten challenge.

Fifteen children with an initial diagnosis of coeliac disease underwent gluten challenge either because they had never had a jejunal biopsy or because they had had one during the first 2 years of life. The challenge was preceded by a biopsy; clinical symptoms, the cellobiose/mannitol permeability test, and gliadin and endomysial antibody measurement were used to determine the timing of the confirmatory biopsy: it was performed if one test result was repeatedly abnormal or two results were concomitantly abnormal. Gliadin antibodies increased early (already 7 days after the reintroduction of gluten to the diet), but in many cases they returned to normal values thereafter. Increased intestinal permeability to sugars and even more positivity of endomysial antibody were good predictors of histologic relapse. The sequential use of laboratory tests during gluten challenge may significantly shorten its duration.

The diagnosis of cow's milk allergy or intolerance (CMAI) is based on clinical improvement on exclusion diet and relapse after challenge with milk. The aim of this work was to investigate the value of the cellobiose/mannitol (C/M) sugar permeability test, performed before and after cow's milk challenge, as a tool for the diagnosis of CMAI. Thirty-two patients underwent milk challenge at a median age of 13 months (range 3-84 months). A dual sugar (C/M) permeability test with an iso-osmolar solution was performed before and 24 h after challenge. Of the 10 patients who developed symptoms after challenge, nine showed increased postchallenge C/M ratio, whereas such an increase was observed in only one of the 22 nonrelapsed subjects. The postchallenge C/M ratio increase in relapsed subjects is to be attributed to both higher cellobiose and lower mannitol urinary excretion. These results suggest the use of the sugar permeability test, in addition to clinical observation, as an aid in the evaluation of provocation tests in infants with suspected CMAI.

The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin‐specific, class II‐restricted T‐cell responses could represent an alternative to current treatments of CD, which are based on a gluten‐free diet. In this study, BALB/c mice derived from a gluten‐free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin‐specific T‐cell proliferation was detected (P < 0.001) after multiple i.n. or i.v. administrations. No significant difference in antibody titre was detected for antigen‐specific immunoglobulin G (IgG) or the IgG1 subclass, but a lower IgG2a‐specific titre was observed. Both interferon‐γ (IFN‐γ) and interleukin (IL)‐2 expression, measured by enzyme‐linked immunosorbent assay (ELISA) and reverse transcription–polymerase chain reaction (RT–PCR), were reduced on antigen administration, both i.v. and i.n. Neither regimen showed a regulatory effect on IL‐4 production. As T helper 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our data therefore highlight the potential of i.n. and i.v. routes for the design of useful immunomodulatory strategies for CD.

Background-Whole gut lavage is currently used as preparation before radiological or endoscopic examination of the large bowel. Aim-To validate the gut lavage technique for the assessment of mucosal inflammation, by measuring intestinal IgG and interleukin l (IL-1>) in the fluid obtained. Patients-Sixteen children with Crohn's disease (CD), 14 with ulcerative colitis (UC), and 22 age matched controls. Methods-Isotonic, non-absorbable polyethylene glycol based lavage solution was given orally or by nasogastric tube. Clear fluid was collected, filtered, and treated with protease inhibitors. IgG, IL-1" and IL-1 receptor antagonist (IL-1-ra) were measured by sandwich enzyme linked immunosorbent assay (ELISA). Results-In patients with UC and CD, IgG and IL-1" levels were significantly (p<0.001) higher than in controls. A positive correlation (p<005) was found with disease activity scores. IL-l-ra levels were not significantly different in UC and CD, when compared with controls, but the IL-1-ra:IL-1j0 ratio was significantly (p< 0.01) lower in patients with UC and CD, and negatively (p<0.001) correlated with IgG levels in lavage fluid. Conclusions-Gut lavage fluid IgG and IL-1, levels and IL-1-ra:IL-1 ratio may provide objective discrimination between active and inactive disease in children with inflammatory bowel disease. (Gut 1997; 41: 60-65)